NORADRENALINE KABI 1 mg/ml CONCENTRATE FOR INFUSION SOLUTION

Introduction

Package Leaflet: Information for the Patient

Noradrenaline Kabi 1 mg/ml Concentrate for Solution for Infusion EFG

Norepinephrine Tartrate

Read all of this leaflet carefully before administration of 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 or nurse.
• This medicine has been prescribed for you only. 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, talk to your doctor or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the Package Leaflet:

1. What is Noradrenaline Kabi and what is it used for
2. What you need to know before you are given Noradrenaline Kabi
3. How Noradrenaline Kabi is given
4. Possible side effects
5. How to store Noradrenaline Kabi
6. Contents of the pack and other information

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

Noradrenaline Kabi contains the active substance noradrenaline (norepinephrine) and acts as a vasoconstrictor (causes the blood vessels to narrow).

Noradrenaline is used in adults in emergency situations to increase blood pressure to normal levels.

2. What you need to know before you are given Noradrenaline Kabi

Noradrenaline Kabi must not be given to you

• if you are allergic to noradrenaline or any of the other ingredients of this medicine (listed in section 6),

• if you have low blood pressure caused by low blood volume,
• if you are being given the anaesthetic gases halothane or cyclopropane, as they may increase the risk of irregular heartbeats.

Warnings and precautions

Tell your doctor or nurse before Noradrenaline Kabi is given to you if:

• you have diabetes
• you have liver or kidney problems
• you have high blood pressure
• you have an overactive thyroid gland
• you have low oxygen levels in your blood
• you have high carbon dioxide levels in your blood
• you have high pressure inside your skull (intracranial pressure)
• you have blood clots or blockages in the blood vessels supplying your heart, intestines or other parts of your body
• you have low blood pressure following a heart attack
• you have angina (chest pain), especially Prinzmetal's angina
• you have significant left ventricular dysfunction
• you have recently had a heart attack
• you have heart rhythm disorders (your heart beats too fast, too slow or irregularly), you may need a reduced dose
• you are elderly

During the infusion of noradrenaline, your doctor will continuously monitor your blood pressure, heart rate and the infusion site.

Children and Adolescents

The safety and efficacy of noradrenaline in children and adolescents under 18 years have not been established. Therefore, its use in children and adolescents is not recommended.

Other medicines and Noradrenaline Kabi

Tell your doctor if you are taking, have recently taken or might take any other medicines.

It is especially important if you are using or have recently used any of the following medicines:

• medicines for depression called "monoamine oxidase inhibitors", if you are taking them now or have taken them in the last 14 days
• medicines for depression called "tricyclic antidepressants" (e.g. imipramine or desipramine)
• linezolid (an antibiotic)
• anaesthetics (especially anaesthetic gases such as cyclopropane, halothane, chloroform, enflurane)
• adrenergic-serotoninergic medicines, e.g. used in the treatment of asthma and heart diseases
• medicines for high blood pressure (e.g. guanethidine, guanadrel, reserpine, methyldopa, alpha and beta blockers)
• rauwolfia alkaloids
• medicines for heart rhythm disorders
• cardiac glycosides (for heart diseases)
• levodopa (for Parkinson's disease)
• thyroid hormones
• oxytocin (used to improve uterine contractions)
• antihistamines (for allergy treatment, e.g. chlorpheniramine hydrochloride, tripelennamine hydrochloride)
• amphetamines
• doxapram (for respiratory disorders)
• mazindol (for obesity treatment)
• medicines for migraine (ergot alkaloids)
• lithium (for certain mental disorders)
• vasopressin, desmopressin (antidiuretics, to reduce urine production)

The use of noradrenaline with propofol (an anaesthetic) may cause propofol infusion syndrome (PRIS), a serious condition affecting patients under sedation with propofol in intensive care units. In this case, the doctor may observe disorders in the body's metabolism from blood tests, which may cause kidney failure, heart failure and death.

Pregnancy and Breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before taking this medicine. Noradrenaline Kabi may harm your baby. It is not known whether this medicine is excreted in breast milk. Your doctor will decide whether you should be given Noradrenaline Kabi.

Driving and using machines

You should not drive or use machines if you are affected by the administration of this medicine.

Noradrenaline Kabi contains sodium

This medicine contains 3.4 mg of sodium (a major component of table salt or cooking salt) per ml. This is equivalent to 0.17% of the maximum recommended daily intake of sodium for an adult.

3. How Noradrenaline Kabi is given

Noradrenaline Kabi will be given to you by a doctor or nurse in a hospital. It will first be diluted and then infused into a vein.

The recommended dose of noradrenaline will depend on your condition. The usual dose is between 0.4 and 0.8 mg per hour. Your doctor will determine the correct dose for you.

After you have received the initial dose, your doctor will assess your response and adjust the dose accordingly.

If you are given too much Noradrenaline Kabi

It is unlikely that you will be given too much of this medicine, as it will be given to you in a hospital. However, tell your doctor or nurse if you have any concerns.

The symptoms of an overdose are severe high blood pressure, slow heart rate, severe headache, brain haemorrhage, sensitivity to light, chest pain, pale skin, high fever, excessive sweating, vomiting and fluid in the lungs causing difficulty breathing.

If you have any further questions on the use of this product, ask your doctor or nurse.

4. Possible side effects

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

The frequency of side effects is not known (cannot be estimated from the available data).

Tell your doctor immediately if you experience:

• sudden itchy rash (urticaria), swelling of hands, feet, ankles, face, lips, mouth or throat (which may cause difficulty swallowing or breathing), feeling of fainting,
• pain or swelling at the injection site.

Tell your doctor as soon as possible if you experience:

• anxiety, insomnia, confusion, weakness, psychotic state
• headache, tremor
• increased eye pressure (acute glaucoma)
• decreased or increased heart rate
• irregular heart rhythm
• changes in the electrocardiogram
• a type of life-threatening circulatory failure called "cardiogenic shock"
• weakness of the heart muscle due to intense physical or emotional stress, palpitations, increased heart muscle contractility, acute heart failure
• high blood pressure, decreased oxygen supply to an organ (hypoxia)
• poor blood flow to hands and feet (which may cause coldness, paleness and/or pain in the limbs)
• gangrene (death of tissue)
• reduced blood plasma volume
• difficulty breathing
• nausea, vomiting
• pale skin, skin discoloration, blue-tinged skin, hot flushes or redness of the skin, skin rash, urticaria or itching
• urine retention
• irritation and necrosis (cell death) at the injection site

Your doctor will monitor your blood pressure and blood volume.

Reporting of side effects

If you experience any side effects, talk to your doctor or nurse. This includes any possible side effects not listed in this leaflet.

You can also report side effects directly via the Spanish Medicines Agency's website: www.notificaRAM.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Noradrenaline Kabi

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

Do not store above 25°C. Store the ampoule in the outer carton to protect it from light.

Do not use this medicine if you notice it has a brown colour or contains visible particles.

Do not use this medicine after the expiry date which is stated on the label of the ampoule and the carton after "EXP". The expiry date refers to the last day of the month shown.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Contents of the pack and other information

What Noradrenaline Kabi contains

• The active substance is noradrenaline (norepinephrine).

Each ml of concentrate for solution for infusion contains 1 mg of noradrenaline base equivalent to 2 mg of noradrenaline tartrate.

Each ampoule with 1 ml of concentrate for solution for infusion contains 1 mg of noradrenaline base equivalent to 2 mg of noradrenaline tartrate.

Each ampoule with 4 ml of concentrate for solution for infusion contains 4 mg of noradrenaline base equivalent to 8 mg of noradrenaline tartrate.

Each ampoule with 5 ml of concentrate for solution for infusion contains 5 mg of noradrenaline base equivalent to 10 mg of noradrenaline tartrate.

Each ampoule with 8 ml of concentrate for solution for infusion contains 8 mg of noradrenaline base equivalent to 16 mg of noradrenaline tartrate.

Each ampoule with 10 ml of concentrate for solution for infusion contains 10 mg of noradrenaline base equivalent to 20 mg of noradrenaline tartrate.

• The other ingredients are: sodium chloride, sodium hydroxide (for pH adjustment), hydrochloric acid (for pH adjustment), water for injections.

Appearance and pack contents:

This medicine is presented as a concentrate for solution for infusion. The solution is clear, colourless to pale yellow.

Transparent glass ampoules containing:

1 ml of concentrate (in packs of 5, 10 or 50);

4 ml, 5 ml, 8 ml and 10 ml of concentrate (each in packs of 5 or 10).

Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder

Fresenius Kabi España, S.A.U

Torre Mapfre-Vila Olímpica

Marina 16-18

08005 Barcelona

Spain

Manufacturer

Labesfal - Laboratórios Almiro, S.A

Zona Industrial do Lagedo

3465-157 Santiago de Besteiros

Portugal

This medicine is authorised in the Member States of the EEA under the following names:

Austria: Noradrenalin Kabi 1 mg/ml Konzentrat zur Herstellung einer Infusionslösung

Belgium: Noradrenaline Kabi 1 mg/ml concentraat voor oplossing voor infusie

Noradrenaline Kabi 1 mg/ml solution à diluer pour perfusion

Noradrenaline Kabi 1 mg/ml Konzentrat zur Herstellung einer Infusionslösung

Cyprus: Noradrenaline/Kabi 1mg/ml concentrate for solution for infusion

Czech Republic: Norepinephrine Kabi

Germany: Noradrenalin Kabi 1 mg/ml Konzentrat zur Herstellung einer Infusionslösung

Denmark: Noradrenalin Fresenius Kabi

Estonia: Norepinephrine Kabi

Greece: Noradrenaline/Kabi

Spain: Noradrenalina Kabi 1 mg/ml concentrado para solución para perfusión EFG

Finland: Noradrenalin Fresenius Kabi 1 mg/ml infuusiokonsentraatti, liuosta varten

France: NORDRENALINE (TARTRATE) KABI 2 mg/ml, solution à diluer pour perfusion

Croatia: Noradrenalin Kabi 1 mg/ml koncentrat za otopinu za infuziju

Hungary: Noradrenaline Kabi 1 mg/ml koncentrátum oldatos infúzióhoz

Ireland: Noradrenaline (Norepinephrine) Kabi 1 mg/ml concentrate for solution for infusion

Italy: Noradrenalina Kabi

Lithuania: Norepinephrine Kabi 1 mg/ml koncentratas infuziniam tirpalui

Latvia: Norepinephrine Kabi 1 mg/ml koncentrats infuziju šķiduma pagatavošanai

Netherlands: Noradrenaline Kabi 1 mg/ml Concentraat voor oplossing voor infusie

Norway: Noradrenalin Fresenius Kabi

Poland: Noradrenaline Kabi

Portugal: Noradrenalina Kabi

Romania: Noradrenalina Kabi 1 mg/ml concentrat pentru soluție perfuzabilă

Sweden: Noradrenalin Fresenius Kabi

Slovenia: Noradrenalin Kabi 1mg/ml koncentrat za raztopino za infundiranje

Slovakia: Norepinephrine Kabi 1 mg/ml

United Kingdom: Noradrenaline (Norepinephrine) Kabi 1 mg/ml concentrate for solution for infusion

Date of last revision of this leaflet:03/2021

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

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The following information is intended for healthcare professionals only:

For intravenous use only after dilution.

The infusion should be given at a controlled rate using either a syringe pump or an infusion pump or a drip system.

Noradrenaline Kabi should be given as a diluted solution and should be administered through a central venous catheter.

If a central venous catheter is not used, whenever possible, the noradrenaline infusion should be given in a large vein, especially an antecubital vein, to minimize the risk of ischaemic necrosis (skin, limbs).

The technique of catheter fixation by ligation should be avoided, if possible, as obstruction of blood flow around the tube may cause stasis and increase the local concentration of the drug.

Incompatibilities

It has been reported that infusion solutions containing noradrenaline tartrate are incompatible with the following substances: iron salts, alkalis and oxidising agents, barbiturates, chlorpheniramine, chlorothiazide, nitrofurantoin, novobiocin, phenytoin, sodium bicarbonate, sodium iodide, streptomycin, sulfadiazine, sulfafurazole.

Instructions for dilution

Add 2 ml of concentrate to 48 ml of diluent for administration via syringe pump or add 20 ml of concentrate to 480 ml diluent for administration via drip system. In both cases, the final concentration of the infusion solution is 40 mg/litre of noradrenaline base (which is equivalent to 80 mg/litre of noradrenaline tartrate). Other dilutions of 40 mg/litre of noradrenaline base may also be used. If other dilutions of 40 mg/litre of noradrenaline base are used, check the calculation of the infusion rate carefully before starting treatment.

The following diluents may be used:

sodium chloride 9 mg/ml (0.9% w/v) infusion with glucose 50 mg/ml (5% w/v)

glucose 50 mg/ml (5% w/v) infusion

sodium chloride 9 mg/ml (0.9% w/v) infusion

Disposal of unused medicine and all materials that have come into contact with it should be done in accordance with local regulations.

Shelf-life after opening of the ampoule:

The medicine should be used immediately after first opening.

Shelf-life after dilution

Chemical and physical stability has been demonstrated for 24 hours at 25°C.

From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions are the responsibility of the user and normally should not be longer than 24 hours at 2°C to 8°C, unless the dilution has been made in controlled and validated aseptic conditions.