NORADRENALINE AGUETTANT 1 mg/ml CONCENTRATE FOR INFUSION SOLUTION

2. What you need to know before you are given Noradrenaline Aguettant Concentrate

Noradrenaline Aguettant should 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 are hypotensive (have low blood pressure) due to hypovolemia (low blood volume);
• if you are taking certain anesthetics such as halothane or cyclopropane (this may increase the risk of irregular heartbeats).

Warnings and precautions

Tell your doctor, pharmacist, or nurse before you are given Noradrenaline Aguettant:

• if you have significant left ventricular dysfunction (heart disease);
• if you have coronary vascular thrombosis (blood clot in the heart), mesenteric (blood clot in the intestine), or peripheral (blood clot in the arm or leg);
• if you have hypotension (low blood pressure) after a heart attack;
• if you have variant angina (Prinzmetal's angina);
• if you have cardiac rhythm disorders during treatment – you may need a reduced dose;
• if you have hyperthyroidism (thyroid problems);
• if you have diabetes mellitus;
• if you are elderly.

Additional monitoring tests you may need to undergo during treatment:

Your blood pressure and heart rate will be monitored frequently during treatment to avoid hypertension (high blood pressure).

Children and adolescents

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

Other medicines and Noradrenaline Aguettant

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

The following medicines may affect the effect of Noradrenaline Aguettant

• Halothane, cyclopropane, chloroform, enflurane, or other halogenated anestheticsare contraindicated (see section 2 of this leaflet, subsection “Noradrenaline Aguettant should not be given to you”): these medicines are anesthetics, cause numbness, and are used before some operations. If you are taking these medicines in addition to noradrenaline, this may increase the risk of irregular heartbeats.
• Amitriptyline, imipramine, trimipramine, moclobemide, iproniazid, phenelzine, fluoxetine, sertraline, desipramine: these medicines are used to treat depression. Taking any of these medicines with noradrenaline may increase its concentration in the blood and therefore its vasoconstrictor effect.
• Digitalis glycosidesmay occasionally cause irregular heartbeats.
• Levodopamay enhance the effects of noradrenaline.
• Antihistamines, as some may block the uptake of catecholamines by peripheral tissues and increase the toxicity of injected noradrenaline.
• Chlorpheniramine hydrochloride, tripelennamine hydrochloride: significantly increase the toxicity of noradrenaline.
• Non-selective MAO inhibitors(or within 14 days after stopping such therapy): increase the pressor action of the sympathomimetic, which is usually moderate. They should only be used under strict medical supervision.
• Selective MAO-A inhibitors: by extrapolation from non-selective MAO inhibitors, risk of increased pressor action. Should only be used under close medical supervision.
• Linezolid, an antibiotic (medicine used to treat infections caused by bacteria and other microorganisms), may increase the concentration of noradrenaline in the blood and therefore its vasoconstrictor effect when taken together.
• Alpha and beta-blockers: if you are taking these medicines in addition to noradrenaline, this may increase the risk of severe hypertension (high blood pressure).
• Thyroid hormones, cardiac glycosides (heart), antiarrhythmic agents: if you are taking these medicines in addition to noradrenaline, this may cause an increase in cardiac effects (heart).
• Alkaloids of ergot or oxytocinmay enhance the vasoconstrictor and vasopressor effects (increase blood pressure).
• Desmopressin or vasopressin: their antidiuretic effect is decreased.
• Lithium: decreases the effect of noradrenaline.
• Guanethidine, guanadrel, reserpine, methyldopa, or tricyclic antidepressants, amphetamine, doxapram, mazindol, alkaloids of rauwolfia: may enhance the effects of noradrenaline.
• Propofol: concomitant administration may cause propofol infusion syndrome (PRIS).

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor for advice before taking this medicine. Noradrenaline may harm the fetus. Your doctor will decide whether you should be given noradrenaline.

It is not known whether this medicine is excreted in breast milk. As many medicines are excreted in breast milk, caution should be exercised when noradrenaline is administered to a breastfeeding woman.

Driving and using machines

As this medicine will be given to you in a hospital, your doctor will inform you when you can drive or use machines.

Noradrenaline Aguettant contains sodium

This medicine contains 3.3 mg of sodium (main component of cooking/table salt) per ml. This is equivalent to 0.16% of the maximum recommended daily intake of sodium for an adult.

3. How Noradrenaline Aguettant Concentrate is given

Noradrenaline Aguettant will be given to you by a doctor or nurse in a hospital.

Dose

Noradrenaline Aguettant is first diluted and then infused into a vein. It must not be mixed with other medicines. The dose of noradrenaline depends on the patient's condition. Your doctor will know what dose is best for you. The initial dose is 0.4 to 0.8 mg per hour of noradrenaline (equivalent to 0.8 to 1.6 mg per hour of noradrenaline tartrate). The dose may then be adjusted using a pump according to the response to treatment, with the aim of establishing normal blood pressure. Your doctor will monitor your blood pressure and blood volume.

If you are given too much Noradrenaline Aguettant

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.

In case of overdose or accidental ingestion, contact the Toxicological Information Service. Telephone (91) 562 04 20.

The symptoms that may occur if you are given too much noradrenaline are severe high blood pressure, slow heart rate, severe headache, sensitivity to light, chest pain, cerebral hemorrhage, paleness, fever, excessive sweating, and vomiting, fluid in the lungs causing difficulty breathing.

If you have any further questions on the use of this product, ask your doctor, pharmacist, 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 unknown (frequency cannot be estimated from the available data).

Tell your doctor or nurse immediatelyif you experience:

• difficulty or irregularity in breathing,
• fast, slow, or irregular heartbeat, palpitations
• chest or throat pain

Tell your doctor or nurse as soon as possible if you experience:

• anxiety, insomnia, confusion, headaches, psychotic state, weakness, tremor, decreased alertness, anorexia, nausea, vomiting
• high blood pressure
• paleness (loss of skin color), sweating, sensitivity to light, gangrene (painful and cold limbs that may turn purple or very dark/black, with tissue necrosis)
• skin necrosis if the infusion is not administered directly into the vein
• acute glaucoma (eye problem)
• skin scarification, bluish discoloration of the skin, hot flashes or skin redness, skin rash, urticaria, or itching
• urinary retention

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist, 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. Storing Noradrenaline Aguettant Concentrate

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 carton and on the label of the ampoule after EXP. The expiry date is the last day of the month shown.

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

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 Aguettant contains

The active substance is noradrenaline (norepinephrine).

Each ml of concentrate for solution for infusion contains 2 mg of noradrenaline tartrate (norepinephrine), equivalent to 1 mg of noradrenaline (norepinephrine).

Each 4 ml ampoule contains 8 mg of noradrenaline tartrate (norepinephrine), equivalent to 4 mg of noradrenaline (norepinephrine).

Each 8 ml ampoule contains 16 mg of noradrenaline tartrate (norepinephrine), equivalent to 8 mg of noradrenaline (norepinephrine).

The other ingredients are sodium chloride, sodium hydroxide, or hydrochloric acid and water for injections.

Appearance and packaging

Clear, colorless, or slightly yellowish solution, pH 3.0 to 4.0, in a 4 ml or 8 ml glass ampoule.

Packs of 10, 50, or 100 ampoules.

Not all pack sizes may be marketed.

Marketing Authorisation Holder

Laboratoire Aguettant

1 rue Alexander Fleming

69007 Lyon

France

Manufacturer

Laboratoire Aguettant

1 rue Alexander Fleming

69007 Lyon

France

or

Delpharm Tours

Rue Paul Langevin

37 170 Chambray-Les-Tours

France

or

Haupt Pharma Livron

1 rue Comte de Sinard,

26250 Livron Sur Drome

France

Local Representative:

Aguettant Ibérica S.L.

Baldiri Reixac, 4-8, Torre I, 4º

08028 Barcelona

Spain

This medicine is authorized in the Member States of the European Economic Area (EEA) and in the United Kingdom (Northern Ireland) under the following names:

BE, LU: Noradrenaline (Norepinephrine) Aguettant

NL: Noradrenaline Aguettant

ES: Noradrenalina Aguettant

BG: Noradrenalin Aguettant

DK, FI, IS, NO, SE: Noradrenalin Laboratoire Aguettant

AT, DE: Norepinephrin Aguettant

UK (NI), IE: Noradrenaline (Norepinephrine)

PT: Noradrenalina tartarato Aguettant

IT: Noradrenalina tartrato Laboratoire Aguettant

Date of last revision of this leaflet 02/2025

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

The following information is intended for healthcare professionals only:

Method of administration

Intravenous use only after dilution. For single use.

Infusion should be performed at a controlled rate using a syringe pump, infusion pump, or drip counter.

Instructions for dilution

This product should be visually inspected before administration. Only a clear, colorless, or slightly yellowish solution, free of particles or precipitates, should be used. Do not use ampoules with a pink or darker color than light yellow or those containing a precipitate.

Add 2 ml of Noradrenaline Aguettant to 48 ml of 5% dextrose (or sodium chloride 9 mg/ml (0.9%), or isotonic saline solution with dextrose) for administration via syringe pump.

Or add 20 ml of Noradrenaline Aguettant to 480 ml of 5% dextrose (or sodium chloride 9 mg/ml (0.9%), or isotonic saline solution with dextrose) for administration via drip counter.

When diluted, the final concentration of the infusion solution is generally 40 mg/liter of noradrenaline (equivalent to 80 mg/liter of noradrenaline tartrate).

If other dilutions are used, carefully check the calculation before starting treatment.

In the absence of specific data, this medicine should not be mixed with other medicines.

After dilution: The chemical and physical stability of the diluted product (in 5% dextrose, sodium chloride 9 mg/ml (0.9%), or dextrose in isotonic saline solution) has been demonstrated for 48 hours at 30°C.

However, from a microbiological point of view, the diluted product should be used immediately. If the product is not used immediately, the duration and conditions of use are the responsibility of the user.

Posology

Initial infusion rate:

The initial infusion rate should be between 10 ml/hour and 20 ml/hour (0.16 ml/minute to 0.33 ml/minute). This is equivalent to 0.4 mg/hour to 0.8 mg/hour of noradrenaline (equivalent to 0.8 mg/hour to 1.6 mg/hour of noradrenaline tartrate).

Dose adjustment:

Once the noradrenaline infusion is established, the dose should be adjusted according to the observed pressor effect. There is great individual variability in the dose required to achieve and maintain normotension. The goal should be to establish a normal low systolic blood pressure (100-120 mmHg) or to achieve an adequate mean arterial pressure (greater than 65 to 80 mmHg, depending on the patient's condition).