Vipranop

Patient Information Leaflet

Vipranop 10 micrograms/ml injection solution or infusion solution

noradrenaline tartrate
Please read all of this leaflet carefully before this medicine is administered to you 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, pharmacist or nurse.
• If you get any side effects, including any not listed in this leaflet, tell your doctor or nurse. See section 4.

Contents of this leaflet

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

1. What Vipranop is and what it is used for

This medicinal product contains the active substance noradrenaline (as noradrenaline tartrate) and acts as a
vasoconstrictor (constricts blood vessels).
This medicinal product is intended for use in adults only.
This medicine is used during surgery to restore and maintain stable blood pressure following the drop caused by anaesthesia.

2. What you should know before being given Vipranop

Do not be given Vipranop if:

• you are allergic to noradrenaline or to any of the other ingredients of this medicine (listed in section 6);
• during anaesthesia with cyclopropane or halothane.

Warnings and precautions
Talk to your doctor, pharmacist or nurse before you are given Vipranop:

• if you have ischaemic heart disease (a condition caused by narrowing or blockage of the blood vessels supplying the heart muscle),
• if you have angina (chest pain),
• if you have recently had a myocardial infarction (heart attack),
• if you have blood clots or blockages in the blood vessels supplying the heart, intestines or other parts of the body (vascular disease),
• if you have hypertension (high blood pressure),
• if you have hypotension (low blood pressure) due to hypovolaemia (low blood volume),
• if you have hyperthyroidism (overactive thyroid),
• if you have intracranial hypertension (high pressure in the brain),
• if you have diabetes (a condition characterised by high blood sugar levels over a prolonged period),
• if you are elderly,
• if you have liver problems or severe kidney problems.

During the infusion of noradrenaline, your doctor will continuously monitor your blood pressure,
heart rate (heart rhythm) and the infusion site.
If noradrenaline needs to be administered at the same time as blood or
plasma transfusion, noradrenaline will be given through a separate intravenous line.
For athletes: using this medicine without a therapeutic indication constitutes doping and may
lead to a positive anti-doping test.

Children and adolescents
Vipranop is indicated only for adults. This medicine is not recommended for children and adolescents
under 18 years of age.

Other medicines and Vipranop
Tell your doctor or pharmacist if you are taking, have recently taken or might take any
other medicines. Vipranop may affect or be affected by other medicines.
A number of medicines are known to increase the toxic effects of noradrenaline:

• Certain anaesthetics such as halothane, cyclopropane (anaesthetic gases) and propofol (injectable anaesthetic);
• Antidepressants, specifically serotonergic-adrenergic antidepressants (such as fluoxetine, sertraline), or selective MAO inhibitors (such as moclobemide), or imipraminic antidepressants (such as imipramine, trimipramine), or non-selective MAO inhibitors (such as amitriptyline, iproniazide, phenelzine);
• Linezolid (an antibiotic) (used to treat infections caused by bacteria and other microorganisms);
• Methylene blue (an antidote);
• Medicines to lower blood pressure (such as guanethidine, reserpine, beta-blockers (e.g. propranolol));
• Thyroid hormones, cardiac glycosides (a class of medicines that increase the heart's pumping force and increase the rate of contractions) and antiarrhythmics (medicines used to suppress abnormal heart rhythms) (such as digitalis);
• Ergot alkaloids (such as bromocriptine);
• Medicines that induce contractions (such as oxytocin).

Pregnancy and breastfeeding

If you are pregnant, think you may be pregnant, planning to become pregnant or are breastfeeding, please consult your doctor, pharmacist or nurse before you are given this
medicine.

Pregnancy
Data on the use of noradrenaline in pregnant women are limited. Noradrenaline can cross the placenta, cause strong uterine contractions and reduce placental blood flow, leading to inadequate oxygen supply to the foetus. For this reason, the use of noradrenaline during pregnancy is not recommended unless the benefits to the mother outweigh the potential risks to the foetus. If you are pregnant, your doctor will decide whether you should be given this medicine, as noradrenaline may harm the unborn child.

Breastfeeding
It is not known whether noradrenaline passes into breast milk. Although noradrenaline is not absorbed orally, this medicine should be used with caution during breastfeeding.

Vipranop contains sodium
This medicine contains 71 mg of sodium (the main component of table salt) per 20 ml vial. This corresponds to 3.6% of the maximum daily dietary intake recommended for an adult.
This medicine contains 177 mg of sodium (the main component of table salt) per 50 ml vial. This corresponds to 8.9% of the maximum daily dietary intake recommended for an adult.

3. How Vipranop is administered

This medicine will be administered to you in a hospital setting by a doctor or nurse.
This medicine is given by intravenous infusion (into a vein). An initial bolus dose of the medicine may be injected into a vein before starting the infusion.
During treatment, you will be continuously monitored, and your blood pressure and infusion rate will be carefully controlled.
The recommended dose of Vipranop depends on your medical condition. Your doctor will determine the appropriate dose for you.
If you are given more Vipranop than you should
Since this medicine will be administered to you during surgery by a trained healthcare professional, it is unlikely that you will receive an excessive amount of Vipranop.
However, if you think you have received too much of the medicine, contact a doctor or nurse immediately.
In case of overdose, the following symptoms may occur: headache, hypertension (severe high blood pressure), slow heart rate, cutaneous vasoconstriction (blood vessels narrowing), circulatory collapse (impaired circulation), cerebral haemorrhage (bleeding in the brain), photophobia, chest pain, pallor, fever, profuse sweating, pulmonary edema (excess fluid in the lungs), and vomiting.
If you have any questions about the use of 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 have been reported:

• Anxiety
• Insomnia
• Headache
• Tremor (involuntary muscle contraction)
• Dizziness
• Acute glaucoma (a condition caused by a rapid or sudden increase in pressure within the eye)
• Tachycardia (fast heart rate), bradycardia (slow heart rate), arrhythmia (irregular heartbeat), electrocardiogram changes (a test of heart activity), cardiogenic shock (a severe drop in blood pressure affecting the heart), stress cardiomyopathy (damage to the heart muscle)
• Arterial hypertension (high blood pressure) and tissue hypoxia (reduced oxygen supply to organs), coldness and pallor of limbs and face, cold and painful extremities (gangrene), depletion of plasma volume (reduced amount of plasma (the liquid part of blood) in the body)
• Dyspnea (difficulty breathing)
• Nausea and vomiting
• Urinary retention
• Local reactions: possibility of irritation and necrosis (cellular damage leading to death of tissue cells) at the injection site.

In case of hypersensitivity (allergy) or overdose, the following effects may occur more frequently in association with arterial hypertension (high blood pressure): severe headache, photophobia (abnormal intolerance to visual perception of light), retrosternal pain (chest pain), pallor (pale skin), fever, profuse sweating, vomiting, pulmonary edema (difficulty breathing), arrhythmia (irregular heartbeat), or cardiac arrest.

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 Vipranop

Keep this medicine out of the sight and reach of children.
Store below 25°C. Keep the vial in the outer packaging to protect the medicine from light. Do not freeze.
Do not use this medicine after the expiry date which is stated on the label of the vial after Exp. The expiry date refers to the last day of that month. Your doctor or nurse will check this.
For single use only.
Chemical and physical in-use stability has been demonstrated for 24 hours at 30°C in a polypropylene syringe.
From a microbiological point of view, the product should be used immediately. If not used immediately, the duration and conditions of storage prior to use are the responsibility of the user and should normally not exceed 24 hours at 2–8°C, unless the handling has taken place under controlled and validated aseptic conditions.
This medicine is a clear, colourless solution, practically free from visible particles. The solution should not be used if it appears slightly yellow or pink, or brown in colour, or if it contains particles or a precipitate.
Any unused medicine and waste material derived from this medicine must be disposed of in accordance with local regulations.

6. Package contents and other information

What Vipranop contains

• The active substance is noradrenaline (as noradrenaline tartrate). Each ml of solution contains 10 micrograms of noradrenaline tartrate, equivalent to 5 micrograms of noradrenaline. Each 20 ml vial contains 200 micrograms of noradrenaline tartrate, equivalent to 100 micrograms of noradrenaline. Each 50 ml vial contains 500 micrograms of noradrenaline tartrate, equivalent to 250 micrograms of noradrenaline.
• The other components are: sodium chloride, disodium edetate, hydrochloric acid (for pH adjustment), and water for injections.

Description of the appearance of Vipranop and contents of the pack
This medicine is a clear, colourless solution for intravenous injection and infusion, practically free from visible particles, presented in a 20 ml or 50 ml transparent glass vial closed with a chlorobutyl rubber stopper and an aluminium cap.
Vipranop is available in packs of 1 and 10 vials.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Laboratoire AGUETTANT
1, rue Alexander Fleming
69007 Lyon
France

Other sources of information
More detailed information on this medicine is available on the website of the Italian Medicines Agency (Agenzia Italiana del Farmaco).

The following information is intended exclusively for healthcare professionals:

Qualitative and quantitative composition:
Each ml of injectable or infusion solution contains 10 micrograms of monohydrate noradrenaline tartrate, equivalent to 5 micrograms of anhydrous noradrenaline.
Each 20 ml vial contains 200 micrograms of monohydrate noradrenaline tartrate, equivalent to 100 micrograms of anhydrous noradrenaline.
Each 50 ml vial contains 500 micrograms of monohydrate noradrenaline tartrate, equivalent to 250 micrograms of anhydrous noradrenaline.

Therapeutic indications:
Restoration and maintenance of blood pressure in adults during the perioperative period following hypotension induced by spinal or general anaesthesia.

Dosage and administration:
This formulation is suitable for use in a perioperative setting; the concentration is not appropriate for use in an intensive care setting.
The infusion may be administered via a peripheral venous line either as an intravenous bolus or continuous infusion using a syringe pump, infusion pump, or drip set.
This medicine must not be diluted prior to use: it is supplied ready-to-use and must not be mixed with other medicinal products.
The patient must be closely monitored and continuously supervised during administration of noradrenaline.
Extravasation must be avoided. To prevent the formation of eschars and necrosis at sites of extravasation, the affected area should be infiltrated as soon as possible with 10 ml – 15 ml of saline solution containing 5 mg to 10 mg of phentolamine. The noradrenaline infusion must be discontinued.

Initial rate
The initial infusion dose ranges from 0.04 µg/kg/min to 0.1 µg/kg/min of noradrenaline tartrate (equivalent to 0.02 µg/kg/min to 0.05 µg/kg/min of noradrenaline). An initial intravenous bolus of 10 µg – 20 µg of noradrenaline tartrate (5 µg – 10 µg of noradrenaline) may be administered before starting the infusion, following spinal anaesthesia or induction of general anaesthesia.

Dose titration
Once noradrenaline infusion has been initiated, the dose may be increased or decreased as needed to maintain the target blood pressure during the perioperative period. The dose should be adjusted according to the patient’s age, weight, and clinical condition.
If a rapid increase in blood pressure is required, an intravenous bolus of 10 µg – 20 µg of noradrenaline tartrate (5 µg – 10 µg of noradrenaline) may be administered.

Duration of treatment and monitoring
Noradrenaline administration should continue throughout the perioperative period as long as necessary to maintain adequate blood pressure and tissue perfusion.

Discontinuation of therapy
Infusions should be gradually tapered; abrupt discontinuation should be avoided as it may lead to acute hypotension.

Elderly patients
In general, dosage for elderly patients should be chosen with caution, starting at the lower end of the dosage range, reflecting the greater likelihood of decreased hepatic, renal, or cardiac function and of concomitant diseases or other medicinal therapies.

For complete information on the indication and use, refer to the Summary of Product Characteristics.