NEOATRICÓN

Package leaflet: Information for the user

Neoatricon 1.5 mg/mL solution for infusion

dopamine hydrochloride
Please read all of this leaflet carefully before the child starts taking this medicine because it contains important information for the child.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or nurse.
• If any side effect occurs, including any not listed in this leaflet, tell your doctor or nurse. See section 4.

Contents of this leaflet

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

1. What Neoatricon is and what it is used for

Neoatricon contains the active substance dopamine hydrochloride. Dopamine is a substance naturally present in the body that increases blood pressure by activating specific receptors (targets) capable of causing narrowing of blood vessels.
Neoatricon is used for the treatment of hypotension (low blood pressure) in newborns, infancy, and children and adolescents under 18 years of age.

2. What you should know before your child uses Neoatricon

Your child must not use Neoatricon

• if they are allergic to dopamine hydrochloride or to any of the other ingredients of this medicine (listed in section 6);
• if they have phaeochromocytoma (a tumour of the adrenal gland);
• if they have uncorrected atrial or ventricular tachyarrhythmia (abnormal or irregular heartbeats in the upper or lower chambers of the heart) or ventricular fibrillation (dangerous, irregular and uncoordinated contractions of the lower chambers of the heart);
• if they have an overactive thyroid gland;
• if they are taking anaesthetics based on cyclopropane or halogenated hydrocarbons.

If you are unsure whether any of the conditions listed above apply to your child, consult your doctor.
Warnings and precautions
Talk to your doctor or nurse before using Neoatricon if your child:

• has heart problems;
• is taking or has recently taken monoamine oxidase inhibitors (MAOIs), used for example to treat depression (see section "Other medicines and Neoatricon");
• has or has had peripheral vascular disease (circulation problems in the hands and feet);
• has kidney or liver disease;
• has low blood volume. The doctor will take necessary measures to ensure your child has normal blood volume before administering dopamine hydrochloride;
• has sepsis (a severe bacterial infection);
• has diseases associated with increased pressure in the lung arteries;
• has a certain type of glaucoma (narrow-angle glaucoma).

The doctor will monitor your child for any possible side effects affecting the heart or kidneys during treatment with dopamine hydrochloride.
The doctor will monitor your child's blood pressure and blood flow to reduce the risk of bleeding in the brain.
Neoatricon may increase the risk of infection; therefore, the doctor will closely monitor your child and take preventive measures against infections.
The doctor will gradually reduce the use of Neoatricon to prevent your child from experiencing a drop in blood pressure.
Dopamine hydrochloride may cause changes in your child's blood test results. The doctor may take blood samples to monitor for such changes.
Other medicines and Neoatricon
Inform your doctor or pharmacist if your child is taking, has recently taken, or might take any other medicines, including those not requiring a prescription.
Special attention is needed if your child is taking other medicines, as some of them may interact with Neoatricon, for example:

• anaesthetics;
• certain medicines used to treat diabetes (e.g. repaglinide, sulfonylureas, etc.). Dopamine hydrochloride may increase blood glucose levels and interfere with antidiabetic medicines;
• certain medicines used to treat depression (tricyclic antidepressants), such as amitriptyline, desipramine, doxepin, imipramine, nortriptyline;
• monoamine oxidase inhibitors (MAOIs), a type of medicine used to treat depression, such as selegiline, isocarboxazide, phenelzine, tranylcypromine, rasagiline, linezolid;
• phenytoin, a medicine used to treat epilepsy;
• alpha and beta-blockers (medicines often used to treat high blood pressure and heart conditions), such as doxazosin, prazosin, terazosin, acebutolol, atenolol, bisoprolol, metoprolol, gadolinium, nebivolol, propranolol;
• ergotamine, a medicine used to treat headache;
• metoclopramide, a medicine used to treat nausea and vomiting;
• guanethidine, a medicine used to treat hypertension (high blood pressure);
• diuretics (medicines that increase urine production), such as bumetanide, torasemide, and furosemide.

If your child is taking any of the medicines listed above, consult your doctor for further information on possible consequences of these interactions.
Pregnancy and breastfeeding
Neoatricon is indicated for use in children. If you are pregnant, suspect you may be pregnant, planning a pregnancy, or breastfeeding, consult your doctor before using this medicine.
If you are a woman of childbearing age, you should use an effective contraceptive method during treatment with Neoatricon. Neoatricon is not recommended during pregnancy.
However, your doctor will prescribe this medicine only if the expected benefits outweigh the potential risks to the unborn child.
It is not known whether Neoatricon is excreted in breast milk. However, since Neoatricon is rapidly eliminated from the body, you may use the medicine while breastfeeding.
Driving and operating machinery
Do not drive or operate machinery while receiving this medicine.
Neoatricon contains sodium metabisulfite
Rarely, this excipient may cause severe hypersensitivity reactions (severe allergy) and bronchospasm (excessive and prolonged contraction of the airway muscles, leading to breathing difficulties).
This medicine contains less than 23 mg of sodium per dose, i.e. it is essentially "sodium-free".

3. How to use Neoatricon

Posology and method of administration
The doctor will determine the most appropriate dose for the child. The dose will depend on the child's health condition and body weight. The infusion rate will be carefully monitored and adjusted according to the child's response.
This medicine will be administered by intravenous infusion (drip) into a large vein under the supervision of a doctor. In newborns, the medicine may also be administered into the umbilical cord.
The child's breathing, blood pressure, oxygen levels, kidney function, and other vital signs will be closely monitored during administration of Neoatricon.
If the child's blood volume is low, a blood transfusion or a "plasma expander" (fluids that increase circulating blood volume) may be given before administering this medicine.
Inform the doctor or nurse if the child experiences burning, pain, or swelling at the site surrounding the intravenous needle during administration of dopamine hydrochloride. If the infusion leaks out of the vein into the surrounding tissues, it may cause tissue damage (for example, blistering or tissue necrosis). Inform the doctor immediately if you notice, or if the child experiences, any pain or swelling at the injection site so that appropriate treatment can be administered.
If an excessive or insufficient amount of dopamine hydrochloride is administered
This medicine will be given to the child in a hospital setting under medical supervision. It is unlikely that the child will receive too high or too low a dose. However, inform the doctor or nurse if you have any concerns.

4. Possible side effects

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

Serious adverse reactions
If you notice any changes in how the child feels during or after treatment, inform the doctor immediately:

• severe allergic reaction – the child may develop a sudden itchy rash (urticaria), swelling of the hands, feet, ankles, face, lips, mouth or throat (which may cause difficulty in swallowing or breathing), and may feel a sense of impending faintness (frequency not known);
• gangrene (decay and death of tissue, in which a change in skin colour may be observed, possibly turning even black) (uncommon frequency);
• severe palpitations (frequency not known); ventricular tachycardia progressing to ventricular fibrillation (uncommon).

These are serious side effects. The child may require urgent medical attention.

Other adverse reactions
If any of the following occur, inform the doctor as soon as possible.

Common side effects (may affect up to 1 in 10 people):

• sinus tachycardia (increased heart rate);
• palpitations (a pounding, rapid or irregular heartbeat);
• anginal pain (a type of chest pain caused by reduced blood flow to the heart);
• ectopic heartbeat (a change in heartbeat that is otherwise normal);
• dyspnoea (shortness of breath);
• hypotension (low blood pressure);
• vasoconstriction (narrowing of blood vessels);
• nausea;
• vomiting;
• headache.

Uncommon side effects (may affect up to 1 in 100 people):

• hypertension (high blood pressure);
• abnormalities in electrocardiogram (a recording of the electrical activity of the heart – aberrant conduction);
• mydriasis (dilation of the pupil);
• bradycardia (low heart rate);
• azotemia (abnormally high levels in the blood of nitrogen-containing compounds such as urea);
• episodes of abnormally fast heart rate (supraventricular tachycardia and ventricular tachycardia);
• very rapid contractions of the lower heart chambers, making the heart unable to pump blood effectively (ventricular fibrillation);
• piloerection (goosebumps);
• gangrene (decay and death of tissue);
• cutaneous necrosis (skin tissue death).

Frequency not known (frequency cannot be estimated from the available data):

• increased risk of bleeding after abdominal surgery or in patients with a tendency to gastrointestinal bleeding (stomach and intestine);
• increased hypoxaemia (low oxygen levels in the blood) in ventilator-dependent patients;
• decreased renal blood flow at higher doses due to vasoconstriction;
• infection;
• suppression of pituitary function;
• local necrosis due to extravasation (leakage of the infusion from the vein causing damage to surrounding tissue).

Reporting of side effects
If the child experiences any side effect, including those not listed in this leaflet, consult a doctor.
You can also report side effects directly via the national reporting system detailed in Annex V.*
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Neoatricon

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the vial label and on the
box after "Exp.". The expiry date refers to the last day of that month.
This medicine does not require any special storage temperature. Store the
vials in the cardboard box to protect the medicine from light.
Neoatricon is available only in single-use vials. After first opening, the medicine must
be used immediately. Any unused medicine must be discarded.
Do not use this medicine if you notice that the solution is cloudy, turbid or discoloured.

6. Package contents and other information

What Neoatricon contains
The active substance is dopamine hydrochloride.
Neoatricon 1.5 mg/mL solution for infusion
Each millilitre of solution contains 1.5 milligrams of dopamine hydrochloride. Each vial contains 45 mg of dopamine hydrochloride in 30 mL.
The other components are sodium metabisulfite (E223) (see section 2 "Neoatricon contains sodium metabisulfite"), water for injections, sodium hydroxide (for pH adjustment), and diluted hydrochloric acid (for pH adjustment).

Description of the appearance of Neoatricon and contents of the pack
Neoatricon solution for infusion is a clear, colourless or pale yellow solution. It is supplied in a clear glass vial with a rubber stopper and an aluminium seal with a tear-off strip.
Number of dosage units
Neoatricon 1.5 mg/mL is supplied as a 30 mL vial, packed in an outer carton.

Marketing Authorisation Holder
BrePco Biopharma Limited
Suite One, The Avenue, Beacon Court
Sandyford
Dublin D18 HX31
Ireland

Manufacturer
Pharmacox Healthcare Ltd.
KW20A Kordin Industrial Park
Paola PLA3000
Malta

More detailed information on this medicinal product is available on the European Medicines Agency website: http://www.ema.europa.eu.
<------------------------------------------------------------------------------------------------------------------------>
The following information is intended for healthcare professionals only.
Infusion of dopamine hydrochloride solution should be initiated at a rate of 5 µg/kg/min and gradually increased in increments of 5 µg/kg/min. The recommended dose range is 5–10 µg/kg/min. If clinically justified, doses higher than 10 µg/kg/min may be administered, up to a maximum of 20 µg/kg/min.
The infusion rate can be calculated using the following formula:
[Dose (μg/kg/min) x Body weight (kg) x 60 (min/hour)]
Infusion rate (mL/hour) = __________________________________________
Concentration (μg/mL)

Instructions for use and handling
For intravenous use. Administer via a central line [umbilical venous catheter (UVC), long cannula, or surgical central venous line (CVL)]. If central access is not available, use a cannula in a large vein.
The infusion system must include an appropriate measuring device to control flow rate and speed.
For single use only. Discard any unused medicine.
Do not dilute.
Do not administer if the solution shows any change in colour.
The maximum acceptable duration for administration from a single vial is 24 hours.

Incompatibilities
Neoatricon solution for infusion must not be added to alkaline intravenous solutions, such as sodium bicarbonate. In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.
Avoid combinations containing gentamicin sulfate, cephalothin sodium, neutral cephalothin sodium, or oxacillin sodium, unless all other feasible alternatives have been tried.
Combinations of ampicillin and dopamine in 5% glucose solution are alkaline and incompatible, resulting in degradation of both drugs; therefore, they must not be mixed.
Mixtures of dopamine and amphotericin B in 5% glucose solution are incompatible, as precipitation occurs immediately after mixing.

Storage precautions during use
This medicinal product requires no special storage temperature conditions.
Keep vials in the original cardboard carton to protect from light.

Package leaflet: Information for the user

Neoatricon 4.5 mg/mL infusion solution

dopamine hydrochloride
Please read this leaflet carefully before the child starts using this medicine because
it contains
important information for the child.

• Keep this leaflet. You may need to read it again.
• If you have any questions, consult the doctor or nurse.
• If any adverse reaction occurs, including those not listed in this leaflet, consult the doctor or nurse. See section 4.

Contents of this leaflet

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

1. What Neoatricon is and what it is used for

Neoatricon contains the active substance dopamine hydrochloride. Dopamine is a substance naturally present in the body that increases blood pressure by activating specific receptors (targets) causing blood vessels to constrict.
Neoatricon is used for the treatment of hypotension (low blood pressure) in newborns, infancy, and children and adolescents under 18 years of age.

2. What you need to know before your child uses Neoatricon

Your child must not use Neoatricon

• if they are allergic to dopamine hydrochloride or to any of the other ingredients of this medicine (listed in section 6);
• if they have phaeochromocytoma (a tumour of the adrenal gland);
• if they have uncorrected atrial or ventricular tachyarrhythmia (abnormal or irregular heartbeats in the upper or lower chambers of the heart), or ventricular fibrillation (dangerous, irregular and uncoordinated contractions of the lower heart chambers);
• if they have an overactive thyroid gland;
• if they are taking anaesthetics based on cyclopropane or halogenated hydrocarbons.

If you are unsure whether any of the conditions listed above apply to your child, consult your doctor.
Warnings and precautions
Talk to your doctor or nurse before using Neoatricon if your child:

• has heart problems;
• is taking or has recently taken monoamine oxidase inhibitors (MAOIs), which are used, for example, to treat depression (see section "Other medicines and Neoatricon");
• suffers or has suffered from peripheral vascular disease (circulation problems in the hands and feet);
• has kidney or liver disease;
• has low blood volume. The doctor will take necessary measures to ensure your child has normal blood volume before administering dopamine hydrochloride;
• has sepsis (a severe bacterial infection);
• has conditions associated with increased pressure in the lung arteries;
• suffers from a specific type of glaucoma (narrow-angle glaucoma).

The doctor will monitor your child for any possible adverse effects on the heart or kidneys during treatment with dopamine hydrochloride.
The doctor will monitor your child's blood pressure and blood flow to reduce the risk of bleeding in the brain.
Neoatricon may increase the risk of infection; therefore, the doctor will closely monitor your child and take preventive measures against infections.
The doctor will gradually reduce the use of Neoatricon to prevent your child from experiencing a drop in blood pressure.
Dopamine hydrochloride may cause changes in your child's blood test results. The doctor may take blood samples to monitor for such changes.
Other medicines and Neoatricon
Inform your doctor or pharmacist if your child is taking, has recently taken, or might take any other medicines, including those not requiring a prescription.
Special caution is needed if your child is taking other medicines, as some may interact with Neoatricon, for example:

• anaesthetics;
• certain medicines used to treat diabetes (e.g. repaglinide, sulfonylureas, etc.). Dopamine hydrochloride may increase blood glucose levels and interfere with antidiabetic medicines;
• certain antidepressants (tricyclic antidepressants), such as amitriptyline, desipramine, doxepine, imipramine, nortriptyline;
• monoamine oxidase inhibitors (MAOIs), a type of medicine used to treat depression, such as selegiline, isocarboxazide, phenelzine, tranylcypromine, rasagiline, linezolid;
• phenytoin, a medicine used to treat epilepsy;
• alpha and beta-blockers (medicines often used to treat high blood pressure and heart conditions), such as doxazosin, prazosin, terazosin, acebutolol, atenolol, bisoprolol, metoprolol, gadolinium, nebivolol, propranolol;
• ergotamine, a medicine used to treat migraine headaches;
• metoclopramide, a medicine used to treat nausea and vomiting;
• guanethidine, a medicine used to treat hypertension (high blood pressure);
• diuretics (medicines that increase urine production), such as bumetanide, torsemide, and furosemide.

If your child is taking any of the medicines listed above, consult your doctor for further information on possible consequences of these interactions.
Pregnancy and breastfeeding
Neoatricon is indicated for use in children. If you are pregnant, suspect you may be pregnant, planning a pregnancy, or breastfeeding, consult your doctor before using this medicine.
If you are a woman of childbearing potential, you should use an effective method of contraception during treatment with Neoatricon. Neoatricon is not recommended during pregnancy.
However, your doctor will prescribe this medicine only if the expected benefits outweigh the potential risks to the unborn child.
It is not known whether Neoatricon is excreted in breast milk. However, since Neoatricon is rapidly eliminated from the body, you may use the medicine during breastfeeding.
Driving and operating machinery
Do not drive or operate machinery while receiving this medicine.
Neoatricon contains sodium metabisulfite
Rarely, this excipient may cause severe hypersensitivity reactions (severe allergy) and bronchospasm (excessive and prolonged contraction of airway muscles leading to breathing difficulties).
This medicine contains less than 23 mg of sodium per dose, i.e. it is essentially "sodium-free".

3. How to use Neoatricon

Posology and method of administration
The doctor will determine the most suitable dose for the child. The dose will depend on the child's health condition and body weight. The rate of administration will be carefully monitored and adjusted according to the child's response.
This medicine will be administered by infusion (intravenous drip) into a large vein under the supervision of a doctor. In newborns, the medicine may also be administered into the umbilical cord.
The child's breathing, blood pressure, oxygen levels, kidney function, and other vital signs will be closely monitored during administration of Neoatricon.
If the child's blood volume is low, a blood transfusion or a "plasma expander" (fluids that increase circulating blood volume) may be given before administering this medicine.
Inform the doctor or nurse if the child experiences burning, pain, or swelling at the site surrounding the intravenous needle during administration of dopamine hydrochloride. If the infusion leaks from the vein into the surrounding tissues, it may cause damage (for example, blistering or tissue necrosis). Inform the doctor immediately if you notice, or if the child experiences, any pain or swelling at the injection site so that appropriate treatment can be administered.
If an excessive or insufficient amount of dopamine hydrochloride is administered
This medicine will be given to the child in a hospital setting under the supervision of a doctor. It is unlikely that the child will receive too high or too low a dose. However, inform the doctor or nurse if you have any concerns.

4. Possible side effects

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

Serious adverse reactions
If you notice any changes in how your child feels during or after treatment, inform your doctor immediately:

• severe allergic reaction – your child may develop a sudden itchy rash (urticaria), swelling of the hands, feet, ankles, face, lips, mouth or throat (which may cause difficulty in swallowing or breathing), and may feel a sense of impending collapse (frequency not known);
• gangrene (decay and death of tissue, where you may notice a change in skin colour which can even turn black) (uncommon frequency);
• severe palpitations (frequency not known); ventricular tachycardia up to ventricular fibrillation (uncommon).

These are serious side effects. Your child may need urgent medical attention.

Other adverse reactions
If any of the following occur, inform your doctor as soon as possible.

Common side effects (may affect up to 1 in 10 people):

• sinus tachycardia (increased heart rate);
• palpitations (a pounding, fast or irregular heartbeat);
• angina pain (a type of chest pain caused by reduced blood flow to the heart);
• ectopic heartbeat (a change in heartbeat which is otherwise normal);
• dyspnoea (shortness of breath);
• hypotension (low blood pressure);
• vasoconstriction (narrowing of blood vessels);
• nausea;
• vomiting;
• headache.

Uncommon side effects (may affect up to 1 in 100 people):

• hypertension (high blood pressure);
• abnormalities in electrocardiogram (a recording of the electrical activity of the heart – aberrant conduction);
• mydriasis (dilation of the pupil);
• bradycardia (slow heart rate);
• azotaemia (abnormally high levels in the blood of nitrogen-containing compounds such as urea);
• episodes of abnormally fast heart rate (supraventricular tachycardia and ventricular tachycardia);
• very rapid contractions of the lower heart chambers, making the heart unable to pump blood effectively (ventricular fibrillation);
• piloerection (goosebumps);
• gangrene (decay and death of tissue, where a change in skin colour may be noticed which can even turn black);
• skin necrosis (tissue death).

Not known (frequency cannot be estimated from the available data):

• increased risk of bleeding after abdominal surgery or in patients with a tendency to gastrointestinal bleeding (stomach and intestine);
• increased hypoxaemia (low blood oxygen levels) in ventilator-dependent patients;
• decreased renal blood flow at higher doses due to vasoconstriction; infection; suppression of pituitary function; local necrosis due to extravasation (leakage of infusion from the vein causing damage to surrounding tissue).

Reporting of side effects
If your child experiences any side effect, including those not listed in this leaflet, talk to your doctor. You can also report side effects directly via the national reporting system detailed in Annex V*. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Neoatricon

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the label of the vial and on the
carton after “Exp.”. The expiry date refers to the last day of that month.
This medicine does not require any special storage temperature. Store the vials in the cardboard carton to protect the medicine from light.
Neoatricon is available only in single-use vials. After first opening, the medicine must be used immediately. Any unused medicine must be discarded.
Do not use this medicine if you notice that the solution is cloudy, turbid or discoloured.

6. Package contents and other information

What Neoatricon contains
The active substance is dopamine hydrochloride.
Neoatricon 4.5 mg/mL solution for infusion
Each millilitre of solution contains 4.5 milligrams of dopamine hydrochloride. Each vial contains
225 mg of dopamine hydrochloride in 50 mL.
The other components are sodium metabisulfite (E223) (see section 2, "Neoatricon contains
sodium metabisulfite"), water for injections, sodium hydroxide (for pH adjustment), and diluted
hydrochloric acid (for pH adjustment).
Description of the appearance of Neoatricon and contents of the pack
Neoatricon solution for infusion is a clear, colourless or pale yellow solution. It is supplied in a clear
glass vial with a rubber stopper and an aluminium seal.
Number of dosage units
Neoatricon 4.5 mg/mL is supplied as a single 50 mL vial, packaged in an outer carton.
Marketing Authorisation Holder
BrePco Biopharma Limited
Suite One, The Avenue, Beacon Court
Sandyford
Dublin D18 HX31
Ireland
Manufacturer
Pharmacox Healthcare Ltd.
KW20A Kordin Industrial Park
Paola PLA3000
Malta
More detailed information on this medicinal product is available on the European Medicines Agency
website: http://www.ema.europa.eu.
<------------------------------------------------------------------------------------------------------------------------>
The following information is intended for healthcare professionals only.
Infusion of dopamine hydrochloride solution should be initiated at a rate of 5 µg/kg/min and
gradually increased in increments of 5 µg/kg/min. The recommended dose range is 5–10 µg/kg/min.
If clinically justified, doses higher than 10 µg/kg/min may be administered up to a maximum of
20 µg/kg/min.
The infusion rate can be calculated using the following formula:
[Dose (μg/kg/min) x Weight (kg) x 60 (minutes/hour)]
Infusion rate (mL/hour) = __________________________________________
Concentration (μg/mL)
Instructions for use and handling
For intravenous use. Administer via a central line [umbilical venous catheter (UVC), long cannula, or
surgical central venous line (CVL)]. If central access is not available, use a large vein cannula.
The infusion system must include an appropriate measuring device to control rate and flow.
For single use only. Discard any unused portions of the medicinal product.
Do not dilute.
Do not administer if the solution shows any discolouration.
The maximum acceptable duration for single administration of a vial is 24 hours.
Incompatibilities
Neoatricon solution for infusion must not be added to alkaline intravenous solutions, such as
sodium bicarbonate. In the absence of compatibility studies, this medicinal product must not be
mixed with other medicinal products.
Avoid combinations containing gentamicin sulfate, cephalothin sodium, neutral cephalothin sodium,
or oxacillin sodium, unless all other feasible alternatives have been exhausted.
Mixtures of ampicillin and dopamine in 5% glucose solution are alkaline and incompatible, resulting
in degradation of both drugs; therefore, they must not be mixed.
Mixtures of dopamine and amphotericin B in 5% glucose solution are incompatible, as a precipitate
forms immediately after mixing.
Storage precautions during use
This medicinal product requires no special temperature storage conditions.
Keep vials in the original cardboard box to protect from light.