Norepinephrine tartrate S.A.L.F.

Package leaflet: Information for the user

NORADRENALINA TARTRATO S.A.L.F. 2 mg/ml concentrate for solution for infusion

Tartrate of Noradrenaline Equivalent medicine
Please read this leaflet carefully before 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, because it could be dangerous.
• If you experience any side effects, including those not listed in this leaflet, contact your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet:

1. What NORADRENALINA TARTRATO S.A.L.F. is and what it is used for
2. What you need to know before using NORADRENALINA TARTRATO S.A.L.F.
3. How to use NORADRENALINA TARTRATO S.A.L.F.
4. Possible side effects
5. How to store NORADRENALINA TARTRATO S.A.L.F.
6. Contents of the pack and other information

1. What NORADRENALINA TARTRATO S.A.L.F. is and what it is used for

NORADRENALINA TARTRATO S.A.L.F. contains the active substance noradrenaline, which belongs to a group of medicines called adrenergic and dopaminergic agents.
NORADRENALINA TARTRATO S.A.L.F. is used in emergency situations for resuscitation in the case of 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 NORADRENALINA TARTRATO S.A.L.F.

Do not use NORADRENALINA TARTRATO S.A.L.F.

• if you are allergic to noradrenaline tartrate or to any of the other ingredients of this medicine (listed in section 6);
• if you have low blood pressure (hypotension) caused by low circulating blood volume;
• if you are pregnant or breastfeeding unless after careful evaluation by your doctor (See section Pregnancy and breastfeeding).

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before NORADRENALINA TARTRATO S.A.L.F. is administered to you.
This medicine must be administered with great caution in the following cases:

• if you are being treated with medicines for depression (tricyclic antidepressants or MAO inhibitors);
• if you are undergoing surgery and will receive anesthesia with halothane or cyclopropane;
• if you have circulatory problems such as thrombosis, a disease causing circulatory problems due to blood clot formation (thrombi);
• if you have low levels of oxygen in the blood;
• if you are elderly.

This medicine will be administered intravenously by a doctor or nurse. The infusion should preferably be given into large-caliber veins of the arm or leg, taking care at the injection site to avoid 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, this medicine should not be injected into leg veins, as there is a risk of developing tissue damage (tissue necrosis).
For individuals engaged in sports, the use of this medicine without genuine therapeutic need constitutes doping and may lead to a positive result in anti-doping tests.

Other medicines and NORADRENALINA TARTRATO S.A.L.F.
Inform your doctor, pharmacist, or nurse if you are taking, have recently taken, or might take any other medicine.
Inform your doctor if you are taking the following medicines, as noradrenaline should not be administered simultaneously:

• medicines used during anesthesia such as cyclopropane and halothane;
• medicines for depression such as tricyclic antidepressants and MAO inhibitors, because they can enhance the effects of noradrenaline, causing an increase in blood pressure or changes 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 severe increase in blood pressure;
• linezolid, an antibiotic used to treat infections, because it may cause a severe 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 injected intravenously together with the following medicines:

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

Fertility, Pregnancy and Breastfeeding
If you are pregnant, suspect you may be pregnant, planning a pregnancy, or breastfeeding, consult your doctor, pharmacist, or nurse before this medicine is administered.
This medicine should not be used during pregnancy unless absolutely necessary, for example in life-saving emergency situations related to heart problems. Noradrenaline may cause harm to the fetus.
Use this medicine with caution if you are breastfeeding, as it is unknown 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.

NORADRENALINA TARTRATO S.A.L.F. contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per 1 ml of injectable solution, i.e. essentially 'sodium-free'.

3. How to use NORADRENALINE TARTRATE S.A.L.F.

This medicine will be administered to you in hospital by trained healthcare personnel. If you have any doubts, please consult your doctor or nurse.
The dose will be determined by the doctor according to your health condition.
This medicine is administered by intravenous infusion (intravenous infusion) after appropriate dilution.
The doses reported below are expressed as noradrenaline base.
The initial dose is 8–12 micrograms per minute via intravenous infusion. The infusion rate will be adjusted to maintain blood pressure at normal values (systolic pressure 80–100 mmHg).
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, the infusion should be started at the lowest possible dose, which may be subsequently increased according to the patient's needs. In elderly patients, infusion into leg veins should be avoided.

If you use more NORADRENALINE TARTRATE S.A.L.F. than you should
Since this medicine will be administered by trained medical staff, it is unlikely that you will receive an excessive dose.
Symptoms of overdose may include headache, marked increase in blood pressure, decrease in heart rate (reflex bradycardia), and heart or circulatory problems.
If you experience any of these symptoms or think you have been given too much of this medicine, contact your doctor or nurse immediately.

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 gets 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 haemorrhage);
• slow heartbeat (bradycardia) or irregular heartbeat (arrhythmias, palpitations);
• chest pain due to heart problems (angina) and cardiac arrest;
• tissue damage at the injection site if the medicine leaks out of the blood vessels (extravasation) during infusion;
• nausea, vomiting, and excessive salivation;
• circulation problems caused by blood clot formation;
• fear, anxiety, agitation, tremor, insomnia;
• confusion, irritability, weakness, and psychosis;
• kidney problems with reduced elimination rate of creatinine and insulin;
• difficulty in urinating;
• breathing difficulties;
• severe headache, light sensitivity, chest pain behind the sternum, pallor, vomiting, and profuse 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, talk to your doctor, pharmacist, or nurse.
You can 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 S.A.L.F.

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 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 S.A.L.F. contains

• The active substance is monohydrate acid tartrate of noradrenaline. Each vial contains 2 mg of monohydrate acid tartrate of noradrenaline (equivalent to 1 mg of noradrenaline base).
• The other components are: sodium chloride, edetate sodium, disodium citrate dihydrate, citric acid monohydrate, sodium hydroxide 45% or hydrochloric acid 37% (pH adjuster), water for injections.

Description of the appearance of NORADRENALINA TARTRATO S.A.L.F. and package contents
Pack containing 5 vials of 1 ml concentrate for solution for infusion.
Marketing Authorization Holder and Manufacturer
S.A.L.F. S.p.A. Laboratorio Farmacologico
via Marconi, 2 - 24069 Cenate Sotto (BG) Italy

The following information is intended exclusively for physicians or healthcare professionals

CLINICAL INFORMATION
Dosage and Administration
Norepinephrine must be diluted in 5% dextrose 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 listed below are expressed as norepinephrine base.
The initial dose of norepinephrine 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 norepinephrine, blood volume depletion should be corrected as completely as possible. However, when norepinephrine is used as an emergency measure to maintain intra-aortic pressure and prevent cerebral or coronary arterial ischemia, it may be administered before or concurrently with blood volume restoration.
Any whole blood or plasma transfusions, if indicated to increase blood volume, must be administered separately from the norepinephrine-containing solution (e.g., using a Y-tube and separate containers if administered simultaneously).
Whenever possible, norepinephrine 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 norepinephrine was infused through an ankle vein.
The infusion site should be monitored frequently. Care must be taken to avoid extravasation of norepinephrine into surrounding 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 vasoconstriction with increased permeability of the venous bed, allowing some leakage. This may also rarely lead 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.

Overdose
An overdose of norepinephrine may cause headache, severe hypertension, reflex bradycardia, marked increase in peripheral resistance, and decreased cardiac output. In case of accidental overdose manifested by excessive elevation of blood pressure, administration of norepinephrine should be suspended until the patient's condition has stabilized.
Norepinephrine-induced bradycardia may be treated with atropine, while hypertensive effects may be counteracted with phentolamine administration.

Incompatibilities
There are conflicting opinions regarding the compatibility of norepinephrine with 0.9% sodium chloride. Indeed, norepinephrine is physically compatible with 0.9% sodium chloride; however, administration of a mixture of norepinephrine diluted solely with saline solution is not recommended, as it does not protect the active substance from oxidation.
Norepinephrine is stable within a pH range of 3.6–6.0; above this range, loss of drug potency may occur. Therefore, the use of norepinephrine in solutions with pH >6 (e.g., containing sodium bicarbonate, barbiturates, alkaline antibiotics) is not recommended.
Norepinephrine is physically incompatible with whole blood; therefore, if the patient is receiving blood transfusions, norepinephrine must be administered separately.
In the absence of incompatibility 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.