Norepinephrine tartrate Galenica Senese

Package leaflet: Information for the user

NORADRENALINE TARTRATE GALENICA SENESE 2 mg/ml

concentrate for solution for infusion
Tartrate noradrenaline
Equivalent medicine
Please read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or nurse.
• This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effect, including those not listed in this leaflet, tell your doctor or nurse. See section 4.

Contents of this leaflet:

1. What NORADRENALINE TARTRATE GALENICA SENESE is and what it is used for
2. What you need to know before using NORADRENALINE TARTRATE GALENICA SENESE
3. How to use NORADRENALINE TARTRATE GALENICA SENESE
4. Possible side effects
5. How to store NORADRENALINE TARTRATE GALENICA SENESE
6. Contents of the pack and other information

1. What NORADRENALINA TARTRATO GALENICA SENESE is and what it is used for

NORADRENALINA TARTRATO GALENICA SENESE contains the active substance noradrenaline, which
belongs to a group of medicines called adrenergic and dopaminergic agents.
NORADRENALINA TARTRATO GALENICA SENESE is used in emergency situations for
resuscitation following cardiac arrest and to restore normal blood pressure in cases of severe and
sudden drop in blood pressure (acute hypotension).

2. What you should know before using NORADRENALINE TARTRATE GALENICA SENESE

Do not use NORADRENALINE TARTRATE GALENICA SENESE

• if you are allergic to noradrenaline tartrate or to any of the other ingredients of this medicine (listed in section 6);
• if you suffer from low blood pressure (hypotension) caused by low circulating blood volume;
• if you suffer from high blood pressure (hypertension) and have chest pain due to heart problems (Prinzmetal's angina);
• if you are due to undergo anesthesia, due to the risk of heart rhythm disturbances (arrhythmias);
• if you are pregnant or breastfeeding (See section on Pregnancy and breastfeeding).

Warnings and precautions
Talk to your doctor or nurse before you are given NORADRENALINE TARTRATE GALENICA SENESE.
This medicine must be administered with particular caution in the following cases:

• if you have recently had a heart attack or suffer from heart disease (ischaemic heart disease);
• if you have high blood pressure (arterial hypertension);
• if you suffer from an overactive thyroid gland (hyperthyroidism);
• if you have diabetes mellitus;
• if you have low circulating blood volume (hypovolaemia) that has not been corrected;
• if you are being treated with medicines for depression (tricyclic antidepressants or MAO inhibitors);
• if you are due to undergo surgery and will receive anesthesia with halothane or cyclopropane;
• if you suffer from circulatory problems such as thrombosis, a condition causing circulatory problems due to blood clot formation (thrombi);
• if you have low levels of oxygen in your blood or high levels of carbon dioxide in your blood;
• if you are allergic to certain food preservatives (sulphites), especially if you suffer from asthma;
• if you are elderly. This medicine will be administered intravenously by a doctor or nurse. Infusion is preferably carried out into large-calibre veins in the arm or leg, with careful attention to the injection site to prevent leakage of the medicine from the injection site (extravasation) and minimize the risk of tissue damage (tissue necrosis). If you are elderly or have occlusive vascular disorders, the medicine should not be injected into leg veins, as there is a risk of developing tissue damage (tissue necrosis).

For athletes: using this medicine without a genuine therapeutic need constitutes doping and may lead to positive results in anti-doping tests.
Children
There is no experience with the use of noradrenaline in children.
Other medicines and NORADRENALINE TARTRATE GALENICA SENESE
Inform your doctor or nurse if you are taking, have recently taken, or might take any other medicines.
Noradrenaline must not be administered together with the following medicines:

• medicines used during anesthesia such as cyclopropane and halothane;
• medicines for depression such as tricyclic antidepressants and MAO inhibitors, because they may enhance the effects of noradrenaline, causing increased blood pressure or disturbances in heart rhythm (cardiac arrhythmias and tachycardia). Inform your doctor or dentist if you are taking these medicines, especially if you are undergoing surgery, including dental procedures. If you experience symptoms of high blood pressure, inform your doctor and discontinue treatment;
• medicines used for mental disorders (neuroleptics), because they may reduce the effects of noradrenaline; if both medicines are administered together, the dose may need to be adjusted to maintain the desired therapeutic effect;
• dihydroergotamine, a medicine used to treat headache, because it may cause a marked increase in blood pressure;
• linezolid, an antibiotic used to treat infections, because it may cause a marked increase in blood pressure;
• entacapone, a medicine used for Parkinson’s disease, because it may cause heart problems (tachycardia, hypertension, arrhythmias);
• guanethidine, a medicine used to treat high blood pressure, because it may cause heart problems (arrhythmias) and increases in blood pressure.

This medicine must not be administered intravenously together with the following medicines:

• certain antibiotics known as basic buffered antibiotics, because noradrenaline is destroyed at pH greater than 6;
• antibiotics and antibacterial agents used against bacteria such as cefamandole, cefoxitin, moxalactam, nitrofurantoin;
• medicines used for epilepsy such as secobarbital, phenobarbital, thiopental.

Noradrenaline enhances the action of other drugs such as atropine, used in anesthesia, digitalis, used to treat heart rhythm disturbances, and anti-asthmatic agents; while it antagonizes the action of certain medicines used to lower blood pressure: beta-blockers, thiazide diuretics, furosemide.
Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, planning a pregnancy, or breastfeeding, consult your doctor or nurse before this medicine is administered.
This medicine must not be administered during pregnancy unless absolutely necessary, for example in life-saving emergency situations due to heart problems. Noradrenaline may cause harm to the fetus.
Use this medicine with caution if you are breastfeeding, as it is not known whether noradrenaline passes into breast milk and there are no available data regarding its effects on the newborn.
Driving and using machines
There are no data available to determine the effect of this medicine on the ability to drive vehicles or operate machinery.
NORADRENALINE TARTRATE GALENICA SENESE contains sodium and sodium metabisulphite
This medicine contains less than 1 mmol (23 mg) of sodium per dose, i.e. it is practically 'sodium-free'.
This medicine contains sodium metabisulphite, which may rarely cause severe hypersensitivity reactions and bronchospasm (particularly in people who suffer from asthma).

3. How to use NORADRENALINE TARTRATE GALENICA SENESE

This medicine will be administered to you in hospital by specialized healthcare personnel. If you have any doubts, consult your doctor or nurse.
The dose will be calculated by the doctor according to your health condition.
This medicine is administered by intravenous infusion (intravenous infusion) after appropriate dilution.
The following doses are expressed as noradrenaline base:
The initial dose is 8–12 micrograms per minute by intravenous infusion. The flow rate will be adjusted so as to maintain blood pressure within normal values (systolic pressure 80–100 mmHg).
The usual maintenance dose ranges from 2 to 4 micrograms per minute, up to a maximum of 68 mg per day.

Use in the elderly
For elderly patients, infusion should start at the lowest possible dose, which may then be increased according to the patient's needs. In elderly patients, infusion into veins of the legs should be avoided.

If you use more NORADRENALINE TARTRATE GALENICA SENESE than you should
This medicine will be administered by specialized personnel; therefore, it is unlikely that you will receive an excessive dose.
Symptoms of overdose may include headache, a marked increase in blood pressure, decreased heart rate (reflex bradycardia), and heart or circulatory problems.
If you experience these symptoms or think that you have been given too much of this medicine, seek immediate advice from your doctor or nurse.

If you have any doubts about how to use this medicine, consult your doctor or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody will experience them.
The following side effects may occur:
Not known (frequency cannot be estimated from the available data)

• increased blood pressure (hypertension);
• fluid accumulation around the lung (pulmonary edema);
• bleeding in the brain (cerebral hemorrhage);
• slow heartbeat (bradycardia) or irregular heartbeat (arrhythmias, palpitations);
• chest pain due to heart problems (angina), stress cardiomyopathy, cardiac arrest; sudden death;
• tissue damage at the injection site if the medicine leaks out of the veins (extravasation) during infusion;
• disturbances in sugar metabolism;
• nausea, vomiting, and excessive salivation;
• blood circulation problems caused by blood clot formation and reduced blood flow to limbs (peripheral ischemia);
• fear, anxiety, agitation, tremor, insomnia;
• confusion, irritability, weakness, and psychosis;
• seizures;
• kidney problems with reduced clearance of creatinine and insulin;
• difficulty urinating;
• breathing difficulties, including absence of breathing (apnea);
• severe headaches, light sensitivity, chest pain behind the sternum, pallor, vomiting, and intense sweating may occur in hypersensitive individuals or following an overdose.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, please inform your doctor or pharmacist.
You may also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store NORADRENALINA TARTRATO GALENICA SENESE

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton after "Expiry".
The expiry date refers to the last day of that month.
Store below 25°C in the original container, tightly closed, protected from light.
Do not refrigerate or freeze. The solution must not be used if it has turned brown or if a precipitate is present.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What NORADRENALINA TARTRATO GALENICA SENESE contains

• The active substance is acid tartrate of noradrenaline. Each vial contains 2 mg of acid tartrate of noradrenaline (equivalent to 1 mg of noradrenaline base).
• The other components are: sodium chloride, sodium metabisulfite, water for injections.

Description of the appearance of NORADRENALINA TARTRATO GALENICA SENESE and contents of the pack
Pack containing 5 and 10 vials of 1 ml concentrate for solution for infusion
Marketing Authorization Holder and Manufacturer
Industria farmaceutica Galenica Senese S.r.l. Via Cassia Nord 351, Monteroni d’Arbia (SI), Italy

Package leaflet: information for the physician

NORADRENALINE TARTRATE GALENICA SENESE 2 mg/ml

concentrate for solution for infusion
Noradrenaline tartrate
The following information is intended exclusively for physicians or healthcare professionals

CLINICAL INFORMATION

Dosage and method of administration
Noradrenaline must be diluted in 5% glucose solution in water or in physiological saline (sodium chloride 0.9%) because these solutions protect against excessive oxidation and the consequent loss of potency. Dilution with saline solution alone is not recommended.

The doses reported below are expressed as noradrenaline base.

The initial dose of noradrenaline is 8–12 micrograms/min by intravenous infusion.
The infusion rate must be adjusted to establish and maintain normal blood pressure (systolic 80–100 mmHg).
The usual maintenance dose ranges from 2 to 4 micrograms/min.
Daily doses up to 68 mg may be required.

Before administering noradrenaline, blood volume depletion should be corrected as completely as possible. However, when, as an emergency measure, intra-aortic pressure must be maintained to prevent cerebral or coronary arterial ischemia, noradrenaline may be administered before or concurrently with blood volume restoration.

Any transfusions of whole blood or plasma, if indicated to increase blood volume, must be administered separately from the solution containing noradrenaline (e.g., using a Y-tube and separate containers if administered simultaneously).

Monitor arterial pressure, heart rate, and electrocardiogram.

Elderly patients
In general, dosage must be carefully selected in elderly patients, usually starting with the lowest dose within the dosing range. In elderly patients, noradrenaline infusion should not be administered into leg veins (see section “Special warnings and precautions for use”).

Special warnings and precautions for use
Use with caution after myocardial infarction, in the presence of ischemic heart disease, arterial hypertension, hyperthyroidism, diabetes mellitus, uncorrected hypovolemia, and in elderly patients.

Whenever possible, noradrenaline infusion should be administered into large-caliber veins, particularly in the antecubital area, as the risk of tissue necrosis appears to be minimal when administered at this site. The femoral vein seems to be another acceptable infusion site. The use of a catheter should be avoided, if possible, since obstruction to blood flow around the tube may cause stasis and increased local drug concentration.

In elderly patients and in patients with occlusive vascular diseases (atherosclerosis, arteriosclerosis, diabetic endarteritis, Buerger's disease), leg veins should be avoided as infusion sites. In such patients, cases of gangrene in the lower extremities have been reported when noradrenaline was infused via an ankle vein.

The infusion site must be frequently checked. Care must be taken to avoid extravasation of noradrenaline into tissues, as tissue necrosis may occur due to the vasoconstrictive action of the drug.

Blanching during infusion, sometimes without evident extravasation, has been attributed to constriction of vessels with increased permeability of the venous bed, allowing some leakage. This may also lead, in rare cases, to tissue loss, particularly during infusion into leg veins in elderly patients or in those suffering from occlusive vascular diseases. Therefore, if blanching occurs, changing the infusion site should be considered.

The solution must be appropriately diluted before intravenous administration. The solution should only be used if clear, colourless, and free from visible particles. It is intended for single, uninterrupted administration and any residual solution must not be used.

Overdose
An overdose of noradrenaline may cause headache, severe hypertension, reflex bradycardia, markedly increased peripheral resistance, and decreased cardiac output. In case of accidental overdose, as indicated by excessive elevation of blood pressure, noradrenaline administration must be suspended until the patient's condition has stabilized.

Bradycardia caused by noradrenaline may be treated with atropine administration, while hypertensive effects may be counteracted by phentolamine administration.

Incompatibilities
There are conflicting opinions regarding the compatibility of noradrenaline with 0.9% sodium chloride. Indeed, noradrenaline is physically compatible with 0.9% sodium chloride, but administration of a mixture of noradrenaline diluted solely with saline solution is not recommended, as it does not protect the active substance from oxidation.

Noradrenaline is stable within a pH range of 3.6–6.0; above this range, there may be a loss of potency of the medicinal product. Therefore, the use of noradrenaline in solutions with pH > 6 (containing sodium bicarbonate, barbiturates, alkaline antibiotics) is not recommended.

Noradrenaline is physically incompatible with whole blood; therefore, when the patient is receiving blood transfusions, noradrenaline must be administered separately.

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.
This medicinal product must not be mixed with other products except glucose solutions or sodium chloride solutions.

For further information, consult the Summary of Product Characteristics.