NORADRENALINE 0.5 mg/ml Solution

Contents of the leaflet

1. Leaflet accompanying the packaging: information for the user
2. Noradrenaline SUN, 0.5 mg/ml, solution for infusion in a pre-filled syringe
   1. Read the leaflet carefully before using the medicine, as it contains important information for the patient.
   2. Table of contents of the leaflet
3. What is Noradrenaline SUN and what is it used for
4. Important information before using Noradrenaline SUN
   1. When not to use Noradrenaline SUN
   2. Warnings and precautions
   3. Children and adolescents
   4. Noradrenaline SUN and other medicines
   5. Pregnancy, breastfeeding and fertility
   6. Pregnancy
   7. Breastfeeding
   8. Fertility
   9. Noradrenaline SUN contains sodium
5. How to use Noradrenaline SUN
   1. Overdose of Noradrenaline SUN
6. Possible side effects
   1. Reporting side effects
7. How to store Noradrenaline SUN
8. Contents of the pack and other information
   1. What Noradrenaline SUN contains
   2. What Noradrenaline SUN looks like and contents of the pack
   3. Marketing authorization holder
   4. Manufacturer/Importer
   5. This medicinal product is authorized in the Member States of the European Economic Area under the following names:
   6. Date of last revision of the leaflet
   7. Information intended for healthcare professionals only:
   8. Qualitative and quantitative composition
   9. Description of the solution
   10. Dosage and administration
   11. Special warnings and precautions for use
   12. Overdose
   13. Pharmaceutical particulars
   14. Reporting suspected adverse reactions

Leaflet accompanying the packaging: information for the user

Noradrenaline SUN, 0.5 mg/ml, solution for infusion in a pre-filled syringe

Noradrenaline
For use in adults.

Read the leaflet carefully before using the medicine, as it contains important information for the patient.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
• If you experience any side effects, including any not listed in this leaflet, please tell your doctor or pharmacist. See section 4.

Table of contents of the leaflet

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

1. What is Noradrenaline SUN and what is it used for

Noradrenaline SUN is a medicine belonging to the group of adrenergic and dopaminergic medicines.
Noradrenaline SUN is indicated for use in the treatment of acute hypotension in patients with shock. This medicine is intended for use only in adult patients.

2. Important information before using Noradrenaline SUN

When not to use Noradrenaline SUN

• if the medicine is administered through a peripheral cannula and/or peripheral vein
• if the patient is allergic to noradrenaline or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

Before starting treatment with Noradrenaline SUN, discuss with your doctor or nurse if:

• the patient has severe left ventricular dysfunction (heart disease)
• the patient has recently had a myocardial infarction (heart attack)
• the patient has arrhythmias (too fast, slow or irregular heartbeat)
• the patient has hyperthyroidism (overproduction of thyroid hormones) or diabetes (elevated blood sugar levels)
• the patient has hypotension (low blood pressure) caused by hypovolemia (decreased blood volume)
• the patient has angina pectoris or any obstruction of blood vessels in the limbs or abdomen (severe difficulties in normal blood flow)
• the patient has a pheochromocytoma (adrenal gland tumor)
• the patient has glaucoma with closed-angle filtration (increased eye pressure caused by blockage of channels through which fluid flows)
• the patient has prostate adenoma (enlargement of the prostate gland)
• the patient has kidney or liver dysfunction (the patient's kidneys or liver do not work properly).

During the infusion of Noradrenaline SUN, the doctor will constantly monitor blood pressure, heart rate (pulse) and the infusion site.
In the event that it is necessary to administer Noradrenaline SUN and perform a blood or plasma transfusion at the same time, the blood or plasma will be transfused in a separate infusion.

Children and adolescents

Noradrenaline SUN is indicated for use only in adults.

Noradrenaline SUN and other medicines

Tell your doctor or pharmacist about all medicines you are taking now or have recently taken, as well as any medicines you plan to take, such as:

• certain inhalation medicines used during anesthesia (halogenated)
• certain antidepressant medicines (imipramine, serotonergic and adrenergic medicines, such as venlafaxine or duloxetine, monoamine oxidase inhibitors, such as moclobemide or phenelzine)
• linezolid (antibiotic)
• methylene blue.

Pregnancy, breastfeeding and fertility

If you are pregnant or breastfeeding, think you may be pregnant or are planning to have a child, consult your doctor or pharmacist before using this medicine.

Pregnancy

There is limited or no data on the use of noradrenaline in pregnant women. Animal studies are insufficient.
Noradrenaline may cross the placenta, cause strong uterine contractions and reduced blood flow through the placenta, which may cause fetal hypoxia. Therefore, Noradrenaline SUN should not be used during pregnancy. This medicine can only be used when the benefits to the mother outweigh the potential risk to the fetus.

Breastfeeding

There is no information on whether noradrenaline passes into breast milk. Breastfeeding should only be done after consulting a doctor.

Fertility

No studies have been conducted in animals, and the effect of this medicine on fertility is unknown. Consult your doctor when planning a pregnancy.

Noradrenaline SUN contains sodium

This medicine contains 180 mg of sodium (main component of common salt) in each pre-filled syringe.
This corresponds to 9% of the maximum recommended daily intake of sodium in the diet for adults.

3. How to use Noradrenaline SUN

Noradrenaline SUN will be administered by a doctor or nurse in a hospital.
Noradrenaline SUN should not be diluted before use: it is a ready-to-use solution in a 50 ml syringe. Noradrenaline SUN will be administered by intravenous infusion (into a vein), exclusively through a central venous catheter, using a syringe pump.
The dose of Noradrenaline SUN depends on the patient's condition. The doctor will know what dose is most suitable.
Noradrenaline SUN should not be used to initiate vasopressor therapy.
The pre-filled syringe will be placed in a syringe pump, which allows the dose to be adjusted according to the response to treatment, in order to establish the correct blood pressure. The infusion site will be regularly monitored.
For single use only. Unused medicine should be discarded.

Overdose of Noradrenaline SUN

In case of overdose, the following symptoms may occur:

• vasoconstriction (narrowing of blood vessels)
• decubitus (ulcers on the skin)
• circulatory collapse (circulatory failure)
• hypertension (high blood pressure).

In case of adverse reactions related to overdose, you should immediately contact your doctor. It is recommended to reduce the dose, if possible.
In case of doubts related to the use of the medicine, you should consult your doctor or nurse.

4. Possible side effects

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

• anxiety
• headache
• tremor (involuntary)
• acute glaucoma (sudden increase in intraocular pressure)
• tachycardia (rapid heartbeat)
• bradycardia (slow heartbeat)
• arrhythmia (irregular heartbeat)
• palpitations
• increased myocardial contractility
• acute heart failure (heart attack)
• hypertension (high blood pressure) and tissue hypoxia (reduced oxygen supply to the organ)
• cold and pale limbs and face
• respiratory failure or difficulty breathing
• shortness of breath (difficulty breathing)
• vomiting
• urinary retention
• locally: possibility of irritation and necrosis (cell damage leading to cell death in tissue) at the injection site.

In the absence of volume replacement, continuous administration of vasopressor therapy to maintain blood pressure may cause the following symptoms:

• marked vasoconstriction of peripheral and visceral vessels (marked narrowing of blood vessels)
• reduced renal blood flow
• reduced urine production
• hypoxia (lack of oxygen in body tissues)
• increased lactate levels in serum (increased lactic acid levels in blood)

In case of hypersensitivity or overdose, the following more frequent side effects may occur:

• hypertension (high blood pressure)
• photophobia (visual perception disorder in the form of light intolerance)
• chest pain
• throat pain
• pallor
• excessive sweating
• vomiting

Reporting side effects

If you experience any side effects, including any not listed in this leaflet, please tell your doctor, pharmacist, or nurse.
Side effects can be reported directly to the Department of Monitoring of Adverse Reactions to Medicinal Products of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products:
Al. Jerozolimskie 181C, 02-222 Warsaw, tel.: 22 49-21-301, fax: 22 49-21-309
Website: https://smz.ezdrowie.gov.pl
Side effects can also be reported to the marketing authorization holder.

5. How to store Noradrenaline SUN

Keep the medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the label of the pre-filled syringe and packaging after "Expiry Date (EXP)". The expiry date refers to the last day of the month.
Do not store above 25°C. Store the pre-filled syringe in the outer carton to protect from light.
Do not use the medicine if the solution is darker than pale yellow or brown, or if it contains particles or sediment.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the pack and other information

What Noradrenaline SUN contains

• The active substance is noradrenaline in the form of noradrenaline tartrate. Each ml of solution contains 1.0 mg of noradrenaline tartrate, which corresponds to 0.5 mg of noradrenaline. Each 50 ml pre-filled syringe contains 50 mg of noradrenaline tartrate, which corresponds to 25 mg of noradrenaline.
• The other ingredients are: sodium chloride, disodium edetate (E 386), butylhydroxyanisole (E 320), hydrochloric acid (to adjust pH), sodium hydroxide (to adjust pH) and water for injections.

What Noradrenaline SUN looks like and contents of the pack

Noradrenaline SUN is a clear, colorless to pale yellow sterile solution, practically free from visible particles in a 50 ml pre-filled syringe.
Noradrenaline SUN is available in a pack containing one protective packaging with one pre-filled syringe containing 50 ml of solution for infusion.
Not all pack sizes may be marketed.

Marketing authorization holder

Sun Pharmaceutical Industries Europe B.V.
Polarisavenue 87
2132 JH Hoofddorp
Netherlands

Manufacturer/Importer

Sun Pharmaceuticals Industries Europe B.V.
Polarisavenue 87
2132 JH Hoofddorp
Netherlands
Terapia S.A.
Str. Fabricii nr.124
400632 Cluj-Napoca
Romania

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

Germany
Noradrenalin SUN
Spain
Noradrenalina SUN
France
Noradrenaline tartrate SUN
Italy
Noradrenalina SUN
Netherlands
Noradrenaline SUN
Romania
Noradrenalină SUN
United Kingdom
Noradrenaline (Norepinephrine)

Date of last revision of the leaflet

Information intended for healthcare professionals only:

This is a fragment of the Summary of Product Characteristics, for use as an auxiliary material during the administration of Noradrenaline SUN. When deciding whether to use the medicine to treat a particular patient, the prescriber should consult the Summary of Product Characteristics for the medicine in question.

Qualitative and quantitative composition

Each ml of solution contains 1.0 mg of noradrenaline tartrate, which corresponds to 0.5 mg of noradrenaline.
Each 50 ml pre-filled syringe contains 50 mg of noradrenaline tartrate, which corresponds to 25 mg of noradrenaline.
Excipients with known effect:
Each ml of solution contains 3.6 mg, which corresponds to 0.16 mmol of sodium.
Each 50 ml pre-filled syringe contains approximately 180 mg, which corresponds to 7.82 mmol of sodium.
List of excipients: sodium chloride, disodium edetate (E386), butylhydroxyanisole (E320), hydrochloric acid (to adjust pH), sodium hydroxide (to adjust pH) and water for injections.

Description of the solution

Clear solution, colorless to pale yellow, practically free from visible particles, in a 50 ml pre-filled syringe.
pH = 3.0–4.0
Osmolality: 270–330 mOsm/kg.

Dosage and administration

For intravenous use only.
Noradrenaline SUN should be administered exclusively as an intravenous infusion through a central venous catheter, to minimize the risk of extravasation leading to tissue necrosis. The infusion of Noradrenaline SUN should be carried out at a controlled rate using an infusion pump.
Noradrenaline SUN should not be diluted before use: it is supplied ready for use. It should not be mixed with other medicines.
Blood pressure monitoring:
During treatment, blood pressure should be closely monitored, preferably by monitoring arterial blood pressure. During treatment with noradrenaline, the patient should be closely monitored.
Dosage
Adults
The concentration of the prepared infusion is 500 mg/l of noradrenaline (1000 mg/l of noradrenaline tartrate).
Initial dose: The initial dose of noradrenaline is usually 0.05 to 0.15 micrograms/kg/min.
Dose adjustment
After starting the infusion of noradrenaline, the dose should be adjusted by 0.05-0.1 μg/kg/min of noradrenaline as a base, according to the observed pressor effect. The dose required to achieve and maintain adequate blood pressure varies from person to person. The goal should be to achieve a low systolic blood pressure in the range of normal values (100–120 mmHg) or to achieve an adequate mean arterial blood pressure (higher than 65–80 mmHg - depending on the patient's condition).

Renal or hepatic impairment
There are no data on the use in patients with renal or hepatic impairment (see section 4.4).
Elderly patients
Elderly patients are particularly sensitive to the effects of sympathomimetic medicines. Therefore, caution should be exercised when administering noradrenaline to elderly patients (see section 4.4).
Children and adolescents
The safety and efficacy of noradrenaline in children under 18 years of age have not been established. Data are not available.
Discontinuation of treatment
The volume of the noradrenaline infusion should be gradually reduced, as sudden discontinuation of treatment may lead to acute hypotension.
Route of administration
For intravenous use.
Method of administration
Noradrenaline SUN 0.5 mg/ml solution for infusion in a pre-filled syringe is diluted and ready for use. It should be used without prior dilution. The product should be administered through a suitable infusion pump with the possibility of precise and continuous administration of the minimum specified volume at a strictly controlled infusion rate, in accordance with the dose adjustment instructions given in section 4.2.
When programming the pump for infusion, select "BD Plastipak" as the syringe setting.

Special warnings and precautions for use

Danger
The use of Noradrenaline SUN is contraindicated in patients with hypotension, in whom circulatory failure is associated with hypovolemia; it is permissible to use this medicine as part of emergency measures to maintain blood flow to the coronary and cerebral arteries until blood transfusion is started.
Noradrenaline SUN is intended for administration by intravenous infusion through a central venous catheter. Therefore, the risk of extravasation leading to tissue necrosis is very limited. The infusion site should be frequently checked. In case of extravasation, the infusion should be discontinued immediately. The infusion site should be immediately infiltrated with phentolamine. The improvement should be closely monitored and re-evaluated to initiate treatment that reverses the effects of ischemia.
Precautions for use
Generally, it is recommended to exercise caution in the following cases of hypotension and hypoperfusion, in which it may be necessary to reduce the dose of noradrenaline:

• significant left ventricular dysfunction associated with acute hypotension. Diagnostics should be initiated in parallel with supportive treatment. Noradrenaline should only be used in patients with cardiogenic shock and refractory hypotension, in particular those with elevated systemic vascular resistance;
• patients with hypotension, in whom coronary thrombosis, venous thrombosis or peripheral vascular obstruction, myocardial infarction or Prinzmetal's angina have been diagnosed. Particular caution should be exercised, as noradrenaline may increase associated ischemia and the risk of infarction;
• patients with arrhythmias during treatment with noradrenaline.

Prolonged administration of potent vasopressor agents may result in a decrease in plasma volume, which should be continuously corrected by adequate hydration and electrolyte supplementation. If plasma volume is not corrected, recurrence of hypotension may occur when the noradrenaline infusion is discontinued, or blood pressure may be maintained, which is associated with the risk of severe peripheral and visceral vasoconstriction and reduced blood flow.
Pheochromocytoma
Caution should be exercised when administering noradrenaline to patients with pheochromocytoma, as it may increase the risk of noradrenaline's effect on the heart.
Glaucoma with closed-angle filtration
Caution should be exercised when administering noradrenaline to patients with glaucoma with closed-angle filtration.
Prostate adenoma
Caution should be exercised when administering noradrenaline to patients with prostate adenoma. In these patients, there may be an increased risk of urinary retention.
Renal or hepatic impairment
There are no data on the use in patients with hepatic or renal impairment. Caution should be exercised when administering sympathomimetic medicines to patients with hepatic or renal impairment, as blood flow to these organs may be reduced.
Hyperthyroidism or diabetes
Caution should be exercised in patients with hyperthyroidism or diabetes.
In cases where it is necessary to administer Noradrenaline SUN at the same time as whole blood or plasma, whole blood or plasma should be transfused in a separate infusion.

Overdose

In case of overdose, the following symptoms may occur: vasoconstriction of the skin, decubitus, circulatory collapse and hypertension.
In case of adverse reactions related to overdose, it is recommended to reduce the dose, if possible.

Pharmaceutical particulars

Incompatibilities
Do not mix this medicine with other medicinal products.
Special precautions for storage
Do not store above 25°C. Store the pre-filled syringe in the outer packaging to protect from light.
Package and packaging
One 50 ml pre-filled syringe made of cyclic olefin copolymer (COP) with a elastomeric closure and a plunger stopper made of bromobutyl, containing 50 ml of solution for injection.
The packaging contains one sachet with a desiccant (a proprietary mixture based on iron).
Each packaging contains one blister, containing one pre-filled syringe.
Instructions for use and disposal
For single use only. Any unused contents should be disposed of.
Noradrenaline SUN is already diluted and ready for use. It should be used without prior dilution. The product should be administered through a suitable infusion pump with the possibility of precise and continuous administration of the minimum specified volume at a strictly controlled infusion rate, in accordance with the dose adjustment instructions given in section 4.2.
Do not use the medicine if the solution is darker than pale yellow or brown, or if it contains particles or sediment.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

Reporting suspected adverse reactions

If you experience any side effects, including any not listed in this leaflet, please tell your doctor, pharmacist, or nurse.
Adverse reactions can be reported directly to the Department of Monitoring of Adverse Reactions to Medicinal Products of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products:
Al. Jerozolimskie 181C, 02-222 Warsaw, tel.: 22 49-21-301, fax: 22 49-21-309
Website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorization holder.