Noradrenaline zentiva

Package leaflet: Information for the patient

Noradrenaline Zentiva, 1 mg/mL, concentrate for solution for infusion
Noradrenaline (Norepinephrine)
Please read all of this leaflet carefully before using this medicine because it contains
important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any further questions, please consult your doctor or nurse.
• If you experience any side effects, including any side effects not listed in this leaflet, please inform your doctor or nurse. See section 4.

Contents of the leaflet

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

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

Noradrenaline Zentiva is a medicinal product containing the active substance noradrenaline (norepinephrine) (as tartrate). It is indicated for use in adult patients in emergency situations to increase arterial blood pressure to normal levels.

2. Important information before using Noradrenaline Zentiva

When not to use Noradrenaline Zentiva

• if the patient is allergic to noradrenaline or any of the other ingredients of this medicine (listed in section 6).
• if the patient has low blood pressure caused by reduced blood volume.
• if the patient is receiving certain inhaled anaesthetics, such as halothane or cyclopropane (which may increase the risk of heart rhythm disorders).
• if the patient is elderly and suffers from arterial blockage or narrowing in the legs.

Warnings and precautions
Before starting treatment with Noradrenaline Zentiva, discuss this with the doctor or
nurse if the patient:

• has diabetes
• has high blood pressure
• has hyperthyroidism (when the thyroid gland produces too much thyroid hormone)
• has low oxygen levels in the blood
• has high carbon dioxide levels in the blood
• has increased intracranial pressure (intracranial pressure)
• has blood clots or blocked blood vessels supplying the heart, intestines, or other parts of the body
• has low blood pressure due to myocardial infarction
• has angina pectoris (chest pain), particularly Prinzmetal's angina
• has severe left ventricular dysfunction
• has recently suffered a myocardial infarction
• has heart rhythm disorders (too fast, too slow, or irregular heartbeat), in which case dose reduction may be necessary
• is elderly
• has impaired liver or kidney function

Children and adolescents
The safety and efficacy of Noradrenaline Zentiva in children and adolescents under 18 years of age have not been established. Therefore, use of this medicine is not recommended in this age group.
Noradrenaline Zentiva and other medicines
Tell the doctor or nurse about all medicines the patient is currently taking or has recently taken, as well as any medicines the patient plans to take. This is particularly important if the patient is taking or has recently taken any of the following medicines:

• medicines used to treat depression called "monoamine oxidase inhibitors" (MAOIs), currently used or used within the last 14 days
• medicines used to treat depression called "tricyclic antidepressants", such as imipramine or desipramine
• medicines affecting adrenergic and serotonergic receptors, e.g. used in the treatment of asthma and heart diseases
• linezolid (an antibiotic)
• anaesthetics (especially inhaled anaesthetics such as cyclopropane, halothane, chloroform, enflurane)
• medicines used to treat high blood pressure (e.g.: guanethidine, reserpine, methyldopa, alpha- and beta-blockers)
• medicines used to treat heart rhythm disorders
• cardiac glycosides (used in the treatment of heart diseases)
• levodopa (used in the treatment of Parkinson's disease)
• thyroid hormones
• oxytocin (used to enhance uterine contractions)
• antihistamines (used in the treatment of allergies)
• amphetamine
• doxapram (used in respiratory disorders)
• mazindol (used in the treatment of obesity)
• medicines used to treat migraine (ergot alkaloids)
• lithium (used in the treatment of certain psychiatric disorders)

Propofol infusion syndrome (PRIS)
Concomitant administration of noradrenaline and propofol (an anaesthetic medicine) may lead to the development of propofol infusion syndrome, a severe condition occurring in patients anaesthetized with propofol in intensive care units. Based on blood tests, the doctor may detect metabolic disturbances in such cases, which may lead to kidney and heart failure and death.
Pregnancy and breastfeeding
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a baby, she should consult a doctor before using this medicine. Noradrenaline may harm the unborn child. The doctor will decide whether Noradrenaline Zentiva should be administered. It is not known whether this medicine passes into human milk. Caution should be exercised when administering noradrenaline to a breastfeeding woman, as many medicines pass into breast milk.
Driving and operating machinery
Patients should not drive or operate machinery while receiving Noradrenaline Zentiva.
Noradrenaline Zentiva contains sodium
Noradrenaline Zentiva medicinal product contains 13.3 mg of sodium (the main component of table salt) in each 4 mL ampoule and 33.3 mg of sodium in each 10 mL ampoule. This corresponds to 0.7% and 1.7% of the maximum recommended daily dietary sodium intake for adults, respectively.

3. How to use Noradrenaline Zentiva

The medicinal product Noradrenaline Zentiva will be administered in a hospital by a doctor or nurse.
Fluids to replenish blood volume will also be given, both before and during the administration of Noradrenaline Zentiva.
This medicine is first diluted and then given as an intravenous infusion.

Dosage
The initial dose of Noradrenaline Zentiva will depend on the patient's condition.
The usual dose is between 0.4 mg and 0.8 mg of noradrenaline per hour. The doctor will determine the appropriate dose for the patient.
After the initial dose is given, the doctor will assess the patient's response to the medicine and adjust the dose accordingly.

Administration
The doctor will frequently check the vein into which Noradrenaline Zentiva is being infused to ensure that the medicine is not leaking into the surrounding tissues, as this could cause a severe skin reaction, particularly when the medicine is administered into a vein in the leg.
Sometimes this medicine may cause the vein to appear paler than usual, which may indicate leakage of Noradrenaline Zentiva into the tissues; in such a case, the doctor may decide to change the infusion site.
If leakage into tissues occurs, the doctor will administer an injection at the leakage site as quickly as possible.

The doctor will monitor the patient's blood pressure and blood volume.

Overdose of Noradrenaline Zentiva
Taking more than the recommended dose is unlikely, as this medicine is administered in a hospital setting.
However, if you have any doubts, you should contact a doctor or nurse immediately.
Symptoms of overdose include very high blood pressure, bleeding into the brain, slow heart rate, severe headache, sensitivity to light, chest pain, pallor, fever, intense sweating, vomiting, and fluid in the lungs causing shortness of breath.

If you have any further questions about the use of this medicine, please consult your doctor or nurse.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone experiences them.
You must inform the doctor immediately if the patient experiences:

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

Other possible adverse reactions include:

• anxiety, insomnia, confusion, weakness, psychotic state
• headache, tremor
• decreased or increased heart rate
• heart rhythm disorders
• abnormal ECG findings
• potentially life-threatening type of circulatory failure, so-called "cardiogenic shock"
• weakening of the heart muscle due to severe physical or emotional stress, palpitations, increased myocardial contractility
• high blood pressure, reduced oxygen supply to certain organs (hypoxia)
• reduced blood flow to hands and feet (cold extremities, pallor and (or) limb pain)
• tissue necrosis (tissue death caused by lack of blood flow or severe bacterial infection)
• decreased blood plasma volume
• breathing difficulties
• pallor, skin scarring, cyanosis (bluish discoloration of the skin), hot flushes or skin redness, skin rash, urticaria or itching
• nausea, vomiting
• urinary retention
• irritation or ulceration at the injection site

Reporting of adverse reactions
If any adverse symptoms occur, including any adverse symptoms not listed in this leaflet, tell your doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring of Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw, Poland
Tel.: + 48 22 49 21 301, Fax: + 48 22 49 21 309, website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorization holder or its representative in Poland.
Reporting adverse reactions helps to provide more information on the safety of the medicine.

5. How to store Noradrenaline Zentiva

Keep the medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton or ampoule after EXP. The expiry date refers to the last day of the specified month.
Store below 25°C. Keep ampoules in the outer packaging to protect from light.
Chemical and physical in-use stability has been demonstrated for 48 hours at 22°C ± 2°C exposed to daylight and at 30°C for the concentrate diluted in 5% glucose solution (w/v), 0.9% sodium chloride solution (w/v), and 0.45% sodium chloride solution (w/v) with 5% glucose solution (w/v).
From a microbiological standpoint, the medicinal product should be used immediately. If not used immediately, the responsibility for storage conditions and duration lies with the user, and it must not exceed 24 hours at 2°C to 8°C, provided that dilution was carried out under controlled and validated aseptic conditions.

6. Contents of the pack and other information

What Noradrenaline Zentiva contains

• The active substance is noradrenaline (norepinephrine). Each mL of concentrate for solution for infusion contains noradrenaline bitartrate equivalent to 1 mg of noradrenaline (norepinephrine). One vial containing 1 mL of concentrate for solution for infusion contains noradrenaline bitartrate equivalent to 1.0 mg of noradrenaline. One vial containing 4 mL of concentrate for solution for infusion contains
  noradrenaline bitartrate equivalent to 4.0 mg of noradrenaline.
  One vial containing 10 mL of concentrate for solution for infusion contains
  noradrenaline bitartrate equivalent to 10.0 mg of noradrenaline.

• Other ingredients: sodium chloride, disodium edetate, sodium hydroxide (for pH adjustment), hydrochloric acid, diluted (for pH adjustment), water for injections.

What Noradrenaline Zentiva looks like and contents of the pack
The concentrate for solution for infusion (sterile concentrate) is a clear, colourless to slightly yellow solution, free from solid particles.
The product is supplied in vials made of colourless type I glass with a capacity of 1 mL, 4 mL or 10 mL, packed in a plastic tray within a cardboard box.
Pack sizes: 10 vials containing 1 mL; 5, 10 or 50 vials containing 4 mL; and 10 vials containing 10 mL.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Zentiva, k.s.
U Kabelovny 130
Dolní Měcholupy
102 37 Prague 10
Czech Republic

Manufacturer
Zentiva, k.s.
U Kabelovny 130
Dolní Měcholupy
102 37 Prague 10
Czech Republic

For further information about this medicinal product, contact the local representative of the Marketing Authorisation Holder:
Zentiva Polska Sp. z o.o.
ul. Bonifraterska 17
00-203 Warsaw
Tel. +48 22 375 92 00

This medicinal product is authorised in the European Economic Area countries under the following names:
Czech Republic: Norepinephrine Zentiva
Denmark, Norway, Sweden: Noradrenalin Zentiva
Poland: Noradrenaline Zentiva
Spain: Noradrenalina Zentiva 1mg/ml concentrado para solución para perfusión EFG

Noradrenaline Zentiva, 1 mg/mL, concentrate for solution for infusion

Information intended exclusively for healthcare professionals:

Intravenous administration.
Route and method of infusion administration
Administer as a diluted solution through a central venous line.
The infusion must be administered at a controlled rate using a syringe pump, infusion pump, or drip counter.

Pharmaceutical incompatibilities:
Pharmaceutical incompatibilities have been reported between infusion solutions containing tartaric acid noradrenaline and the following substances: iron salts, alkalizing and oxidizing agents, barbiturates, chlorpheniramine, chlorothiazide, nitrofurantoin, novobiocin, phenytoin, sodium bicarbonate, sodium iodide, streptomycin, sulfadiazine, sulfafurazole.

Administration and preparation
Dilution instructions
For single use only. Any unused content of the vial should be discarded.
Inspect the solution before use. Do not use this medicine if the solution contains visible particulate matter. Do not use the solution if it is brown in color.

Dilute using one of the following diluents: 5% glucose solution (w/v), 0.9% sodium chloride solution (w/v), or 0.45% sodium chloride solution (w/v) with 5% glucose solution (w/v).

Dilution factor (e.g.):
Add 1 mL of concentrate to 24 mL of diluent.
Add 2 mL of concentrate to 48 mL of diluent.
Add 4 mL of concentrate to 96 mL of diluent.
Add 10 mL of concentrate to 240 mL of diluent.
Add 20 mL of concentrate to 480 mL of diluent.

In each case, the final concentration of the infusion solution is 40 mg/L noradrenaline (equivalent to 80 mg/L tartaric acid noradrenaline). The medicinal product may also be diluted to concentrations other than 40 mg/L noradrenaline. If dilution results in a concentration other than 40 mg/L noradrenaline, the infusion rate must be accurately recalculated before starting treatment.

After dilution:
Chemical and physical stability has been demonstrated for 48 hours at 22°C ± 2°C under exposure to daylight and at 30°C for the concentrate diluted in 5% glucose solution (w/v), 0.9% sodium chloride solution (w/v), and 0.45% sodium chloride solution (w/v) with 5% glucose solution (w/v).

Only clear, colorless solutions free from particulate matter should be used.

From a microbiological standpoint, the medicinal product should be used immediately. If not used immediately, the user is responsible for the storage conditions and duration, which must not exceed 24 hours at 2°C to 8°C, provided that dilution was carried out under controlled and validated aseptic conditions.

Any unused product or waste material should be disposed of in accordance with local regulations.