Noradrenaline sun

Patient Information Leaflet

Noradrenaline SUN, 0.5 mg/ml, solution for infusion in ampoule-syringe
Noradrenalinum
For use in adults.
Please read all of this leaflet carefully before use, as it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, please consult your doctor or nurse.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. This medicine may harm others, even if their symptoms are the same.
• If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor or nurse immediately. See section 4.

Table of contents

1. What Noradrenaline SUN is and what it is used for
2. Important information before use of 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 Noradrenaline SUN is and what it is used for

Noradrenaline SUN is a medicine belonging to the group of adrenergic and dopaminergic agents.
Noradrenaline SUN is indicated for the treatment of acute hypotensive states in patients in shock. This medicine is intended for use in adults only.

2. Important information before using Noradrenaline SUN

When NOT to use Noradrenaline SUN

• if the medicine is administered via a peripheral cannula and (or) into a 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 the doctor or
nurse if:

• the patient has severe left ventricular dysfunction (heart disease)
• the patient has recently suffered a myocardial infarction (heart attack)
• the patient has cardiac arrhythmias (too fast, too slow or irregular heartbeat)
• the patient has hyperthyroidism (overproduction of thyroid hormones) or diabetes (elevated blood sugar (glucose))
• the patient has hypotension (low blood pressure) due to hypovolemia (reduced blood volume)
• the patient has angina pectoris or any vascular occlusion in the limbs or abdomen (severe impairment of normal blood flow)
• the patient has been diagnosed with a phaeochromocytoma (adrenal gland tumour)
• the patient has been diagnosed with closed-angle glaucoma (increased eye pressure due to blockage of fluid drainage channels)
• the patient has benign prostatic hyperplasia (enlargement of the prostate gland)
• the patient has impaired kidney function (the patient's kidneys do not work properly) or liver function (the patient's liver does not work properly).

During Noradrenaline SUN infusion, the doctor will continuously monitor blood pressure, heart rate (pulse) and the infusion site.
If Noradrenaline SUN infusion and blood or plasma transfusion are required simultaneously, the blood or plasma will be administered through a separate intravenous line.
Children and adolescents
Noradrenaline SUN is indicated for use in adults only.
Noradrenaline SUN and other medicines
Inform the doctor or pharmacist about all medicines the patient is currently taking or has recently taken, as well as any medicines the patient plans to take, such as:

• certain inhaled anaesthetics (halogenated agents),
• certain antidepressants (imipramine, serotonergic and adrenergic agents such as venlafaxine or duloxetine, monoamine oxidase inhibitors such as moclobemide or phenelzine),
• linezolid (an antibiotic),
• methylene blue.

Pregnancy, breastfeeding and fertility
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a child, she should consult a doctor or pharmacist before using this medicine.
Pregnancy
There is no or limited amount of data on the use of noradrenaline in pregnant women. Animal studies are insufficient.
Noradrenaline may cross the placenta, cause strong uterine contractions and reduce blood flow through the placenta, which may lead to fetal hypoxia. Therefore, Noradrenaline SUN should not be used during pregnancy. This medicine may be used only if the benefit to the mother outweighs the potential risk to the fetus.
Breastfeeding
It is unknown whether noradrenaline passes into human milk. Breastfeeding should only be considered after consultation with a doctor.
Fertility
Animal studies have not been conducted, and the effect of this medicine on fertility is unknown. Consult a doctor when planning pregnancy.
Noradrenaline SUN contains sodium
This medicine contains 180 mg of sodium (the main component of table salt) in each pre-filled syringe.
This corresponds to 9% of the maximum recommended daily sodium intake in the diet for adults.

3. How to use Noradrenaline SUN

Noradrenaline SUN will be administered by a doctor or nurse in a hospital setting.
Noradrenaline SUN must not be diluted before use: it is a ready-to-use solution in a 50 ml syringe. Noradrenaline SUN will be given as an intravenous infusion (into a vein), exclusively via a central venous catheter, using a syringe pump.
The dose of Noradrenaline SUN depends on the patient's condition. The doctor will determine the most appropriate dose.
Noradrenaline SUN should not be used to initiate vasopressor therapy.
The pre-filled syringe will be placed in a syringe pump, which allows adjustment of the dose according to the treatment response, in order to achieve the correct blood pressure. The infusion site will be monitored regularly.
For single use only. Any unused medicinal product must be discarded.
Overdose of Noradrenaline SUN
In case of overdose, the following symptoms may occur:

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

If adverse effects related to administration of an excessive dose occur, contact a doctor immediately. Dose reduction is recommended, if possible.
If you have any questions about the use of this medicine, consult your doctor or nurse.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
The following adverse reactions have been reported:

• anxiety
• headache
• tremor (involuntary)
• acute glaucoma (rapid increase in pressure inside the eye)
• tachycardia (increased heart rate)
• bradycardia (slowed heart rate)
• arrhythmia (irregular heartbeat)
• palpitations
• increased myocardial contractility
• acute heart failure (heart attack)
• arterial hypertension (high blood pressure) and tissue hypoxia (reduced oxygen supply to organs)
• cold and pale extremities and face
• respiratory failure or breathing difficulties
• dyspnea (difficulty breathing)
• vomiting
• urinary retention
• local reactions: possible irritation and necrosis (cell damage leading to cell death in tissue) at the injection site.

If blood volume is not adequately replenished, continuous administration of this vasoactive medicine to maintain blood pressure may lead to the following symptoms:

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

In cases of hypersensitivity or overdose, the following adverse reactions may occur more frequently:

• arterial hypertension (high blood pressure)
• photophobia (visual disturbances characterized by light intolerance)
• retrosternal pain (chest pain)
• sore throat
• pallor
• excessive sweating
• vomiting

Reporting of adverse reactions
If any adverse reactions occur, including those not listed in this leaflet, inform your doctor, pharmacist, or nurse.
Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions at 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.
Reporting adverse reactions helps to provide more information on the safety of the medicine.

5. How to store Noradrenaline SUN

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

6. Package contents 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, equivalent to 0.5 mg of noradrenaline. Each 50 ml pre-filled syringe contains 50 mg of noradrenaline tartrate, equivalent to 25 mg of noradrenaline.
• The other ingredients are: sodium chloride, disodium edetate (E 386), butylhydroxyanisole (E 320), hydrochloric acid (for pH adjustment), sodium hydroxide (for pH adjustment), and water for injections.

What Noradrenaline SUN looks like and contents of the pack
Noradrenaline SUN is a clear, colourless 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 aluminium protective pouch with one pre-filled syringe containing 50 ml of infusion solution.
Not all pack sizes may be marketed.
Marketing Authorisation Holder
Sun Pharmaceutical Industries Europe B.V.
Polarisavenue 87
2132 JH Hoofddorp
The Netherlands
Manufacturer/Importer
Sun Pharmaceuticals Industries Europe B.V.
Polarisavenue 87
2132 JH Hoofddorp
The Netherlands
Terapia S.A.
Str. Fabricii nr.124
400632 Cluj-Napoca
Romania
This medicinal product is authorised for sale 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)

Information intended exclusively for healthcare professionals:

This is an excerpt from the Summary of Product Characteristics, intended for use as a supplementary
material during the administration of Noradrenaline SUN. When determining whether the use of the
medicinal product is appropriate for the treatment of a specific patient, the prescriber should consult
the Summary of Product Characteristics for this medicinal product.

Qualitative and quantitative composition
Each ml of solution contains 1.0 mg of noradrenaline tartrate, equivalent to 0.5 mg of noradrenaline.
Each 50 ml pre-filled syringe contains 50 mg of noradrenaline tartrate, equivalent to 25 mg of noradrenaline.

Excipients with known effect:
Each ml of solution contains 3.6 mg, equivalent to 0.16 mmol of sodium.
Each 50 ml pre-filled syringe contains approximately 180 mg, equivalent to 7.82 mmol of sodium.

List of excipients: sodium chloride, disodium edetate (E386), butylhydroxyanisole (E320), hydrochloric acid (for pH adjustment), sodium hydroxide (for pH adjustment), and water for injections.

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

Dosage and method of administration
For intravenous use only.
Noradrenaline SUN must be administered exclusively as an intravenous infusion via a central venous catheter to minimize the risk of extravasation leading to tissue necrosis. The Noradrenaline SUN infusion must be administered at a controlled rate using an infusion pump.
Noradrenaline SUN should not be diluted prior to administration: it is supplied ready for use. It must not be mixed with other medicinal products.

Blood pressure monitoring
Blood pressure must be carefully monitored during treatment, preferably by continuous arterial pressure monitoring. Patients must be closely observed during noradrenaline therapy.

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 between 0.05 and 0.15 micrograms/kg/min.

Dose adjustment
After starting the noradrenaline infusion, the dose should be adjusted by increments of 0.05–0.1 μg/kg/min of noradrenaline base, according to the observed pressor effect. The dose required to achieve and maintain adequate blood pressure varies between individuals. The goal should be to achieve a systolic blood pressure within the normal range (100–120 mmHg) or an appropriate mean arterial pressure (above 65–80 mmHg, depending on the patient's condition).

Renal or hepatic impairment
There are no data on the use of noradrenaline in the treatment of patients with renal or hepatic impairment (see section 4.4 of the SmPC).

Elderly patients
Elderly patients are particularly sensitive to the effects of sympathomimetic drugs. Therefore, caution should be exercised when administering noradrenaline to elderly patients (see section 4.4 of the SmPC).

Children and adolescents
The safety and efficacy of noradrenaline in children under 18 years of age have not yet been established. Data are not available.

Discontinuation of treatment
The infusion volume of noradrenaline should be gradually reduced, as abrupt discontinuation of treatment may lead to the occurrence of acute hypotension.

Route of administration
For intravenous administration.

Method of administration
Noradrenaline SUN 0.5 mg/ml infusion solution in pre-filled syringe is diluted and ready for use. It should be used without prior dilution. The medicinal product should be administered using an appropriate infusion pump capable of accurately and continuously delivering minimal defined volumes at strictly controlled infusion rates, according to the dose adjustment instructions provided in the table above.

When programming the infusion pump, select “BD Plastipak” as the syringe setting.

Special warnings and precautions for use

Danger
Noradrenaline SUN is contraindicated in patients with hypotension in whom circulatory collapse is associated with hypovolemia; however, the use of this medicinal product may be acceptable as an emergency measure to maintain blood flow to the coronary arteries and cerebral arteries until blood transfusion is initiated.

Noradrenaline SUN is intended for intravenous infusion only via a central venous catheter. Therefore, the risk of extravasation leading to tissue necrosis is very limited. The infusion site should be checked frequently. In case of extravasation, infusion must be stopped immediately. The site of extravasation should be promptly infiltrated with phentolamine. Careful monitoring of improvement is required, and reassessment should be performed to initiate treatment reversing the effects of ischemia.

Precautions for use
Particular caution is generally recommended in the following cases of hypotension and hypoperfusion, in which reduction of the noradrenaline dose may be necessary:

• Significant left ventricular dysfunction associated with acute hypotension. Supportive treatment should be initiated concurrently with diagnostic procedures. Noradrenaline should be used only in patients with cardiogenic shock and treatment-resistant hypotension, particularly those with elevated systemic vascular resistance;
• Patients with hypotension in whom thrombosis of coronary vessels, mesenteric vessels, or peripheral vessels, myocardial infarction, or Prinzmetal's angina has been diagnosed. Particular caution should be exercised, as noradrenaline may increase associated ischemia and the risk of infarction;
• Occurrence of cardiac arrhythmias during treatment with noradrenaline.

Long-term administration of any potent vasoactive agents may result in reduced plasma volume, which should be continuously corrected by appropriate fluid replacement and electrolyte supplementation. If plasma volume is not corrected, recurrence of hypotension may occur upon discontinuation of noradrenaline infusion, or blood pressure may be maintained at the expense 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 effects on the heart.

Closed-angle glaucoma
Caution should be exercised when administering noradrenaline to patients with closed-angle glaucoma.

Prostatic adenoma
Caution should be exercised when administering noradrenaline to patients with prostatic adenoma. These patients may have an increased risk of urinary retention.

Renal and hepatic impairment
There are no data on the use of noradrenaline in patients with hepatic or renal impairment. Caution should be exercised when administering sympathomimetic drugs 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.

When Noradrenaline SUN must be administered simultaneously with whole blood or plasma, whole blood or plasma should be administered through a separate infusion line.

Overdose
In case of overdose, the following symptoms may occur: vasoconstriction of the skin, decubitus ulcers, circulatory collapse, and arterial hypertension.
In the event of adverse effects related to overdose, dose reduction should be considered whenever possible.

Pharmaceutical data

Incompatibilities
Do not mix this medicinal product with other medicinal products.

Special precautions for storage
Do not store above 25°C. Store the pre-filled syringe in its outer packaging to protect from light.

Nature and contents of container
One 50 ml pre-filled syringe made of cyclic olefin copolymer (COP) with a chlorobutyl rubber closure and a bromobutyl plunger stopper, containing 50 ml of injection solution.
The packaging contains one sachet with an oxygen absorber (proprietary iron-based mixture).
Each pack contains one blister containing one pre-filled syringe.

Instructions for use and disposal
For single use only. Any unused portion should be discarded.
Noradrenaline SUN is already diluted and ready for use. It should be used without prior dilution. The product should be administered via an appropriate infusion pump capable of accurately and continuously delivering minimal defined volumes at strictly controlled infusion rates, according to the dose adjustment instructions provided in section 4.2.

The medicinal product should not be used if the solution is darker than pale yellow or brown, or if it contains particles or precipitate.
Do not use the sterile solution if it is not clear and contains particles, or if the seal of the pre-filled syringe is damaged.
Any unused medicinal product or waste material should be disposed of in accordance with local regulations.

Reporting suspected adverse reactions
If any adverse reactions occur, including any adverse reactions not listed in this leaflet, inform a doctor, pharmacist, or nurse.
Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions, 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.