VIPRANOP 5 micrograms/ml injectable solution and perfusion solution

2. What you need to know before Vipranop is administered to you

Vipranop will not be administered to you:

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

Warnings and precautions

Talk to your doctor, pharmacist or nurse before Vipranop is administered to you:

• if you have ischemic heart disease (disease caused by narrowing or blockage of 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 blood vessels supplying the heart, intestine or other parts of the body (vascular disease),
• if you are hypertensive (have high blood pressure),
• if you are hypotensive (have low blood pressure) due to hypovolemia (low blood volume),
• if you have hyperthyroidism (your thyroid is overactive),
• if you have intracranial hypertension (high pressure in the brain),
• if you are diabetic (disease characterized by high blood sugar levels over prolonged periods),
• if you are an elderly patient,
• if you have liver or severe kidney problems.

During noradrenaline infusion, your doctor will constantly monitor your blood pressure, heart rate and infusion site.

If noradrenaline needs to be administered at the same time as a blood or plasma transfusion, the transfusion will be administered in a separate drip system.

Children and adolescents

Vipranop is only indicated in adults. This medicine is not recommended in 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.

It is known that a number of medicines increase the toxic effects of noradrenaline:

• Certain anesthetics such as halothane, cyclopropane (anesthetic gases) and propofol (injectable anesthetic).
• • Antidepressants, called serotonergic-adrenergic antidepressants (such as fluoxetine, sertraline), or selective monoamine oxidase inhibitors (MAOIs) (such as moclobemide), or imipramine-based antidepressants (such as imipramine, trimipramine) or non-selective MAOIs (such as amitriptyline, iproniazid, phenelzine).
• Antibiotic linezolid (medicine used to treat infections caused by bacteria and other microorganisms).
• Methylthioninium chloride (an antidote).
• Medicines that lower blood pressure (such as guanethidine, reserpine, beta-blockers (e.g. propranolol)).
• Thyroid hormones, digitalis glycosides (a class of medicines that increase cardiac output and increase heart rate), and antiarrhythmic agents such as digoxin (medicines used to suppress abnormal heart rhythms).
• Ergot alkaloids (such as bromocriptine).
• Medicines that induce contractions (such as oxytocin).

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before Vipranop is administered to you.

Pregnancy

There are limited data on the use of noradrenaline in pregnant women. Noradrenaline may pass through the placenta, cause strong uterine contractions and reduce blood flow to the placenta, which makes the fetus receive very little oxygen. For this reason, the use of noradrenaline during pregnancy is not recommended unless the benefits to the mother outweigh the potential risks to the fetus. If you are pregnant, your doctor will decide whether to administer noradrenaline to you, as it may harm the fetus.

Breastfeeding

It is not known whether noradrenaline passes into breast milk. This medicine may be used with caution during breastfeeding since noradrenaline is not absorbed orally.

Vipranop contains sodium

This medicine contains 71 mg of sodium (main component of table/cooking salt) in each 20 ml vial. This is equivalent to 3.6% of the maximum recommended daily intake of sodium for an adult.

This medicine contains 177 mg of sodium (main component of table/cooking salt) in each 50 ml vial. This is equivalent to 8.9% of the maximum recommended daily intake of sodium for an adult.

3. How Vipranop is administered

This medicine will be administered to you in a hospital by a doctor or nurse.

This medicine will be administered by intravenous infusion (into a vein). An initial bolus of the medicine may be injected into the vein before starting the infusion.

During your treatment, your blood pressure will be monitored, the infusion rate will be continuously supervised and you will be constantly monitored.

The recommended dose of Vipranop will depend on your state of health. Your doctor will determine the correct dose for you.

If you are given more Vipranop than you should

It is unlikely that you will receive more medicine than you should, as this medicine will be administered to you during surgery by a trained healthcare professional. However, if you think you have received too much medicine, contact your doctor or nurse immediately.

The following symptoms may occur in case of overdose: headache, severe hypertension (high blood pressure), slow heart rate, skin vasoconstriction (blood vessels narrow), circulatory collapse (circulatory failure), cerebral hemorrhage (stroke), sensitivity to light, chest pain, paleness, fever, excessive sweating, pulmonary edema (difficulty breathing), and vomiting.

If you have any further questions on the use of this medicine, ask 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 (lack of sleep).
• Headache.
• Tremor (involuntary muscle contraction).
• Dizziness.
• Acute glaucoma (condition caused by a rapid and sudden increase in pressure inside the eye).
• Tachycardia (fast heart rate), bradycardia (slow heart rate), arrhythmia (irregular heartbeats), change in electrocardiogram (a test of heart activity), cardiogenic shock (drastic drop in blood pressure in the heart area), stress cardiomyopathy (damage to the heart muscle).
• Hypertension (high blood pressure) and tissue hypoxia (decrease in oxygen supply to some organs), coldness and paleness of limbs and face, painful and cold extremities (gangrene), decrease in plasma volume (reduction in the amount of plasma (the liquid part of the blood) in the body).
• Dyspnea (difficulty breathing).
• Nausea and vomiting.
• Urinary retention.
• Locally: possibility of irritation and necrosis (cell damage, causing cell death in tissue) at the injection site.

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

Reporting of side effects

If you experience any side effects, talk to your doctor, pharmacist or nurse, even if it is not listed in this leaflet. You can also report side effects directly through the Spanish Medicines Monitoring System for Human Use: www.notificaRAM.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Vipranop

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 label of the vial after EXP. The expiry date is the last day of the month stated.

Store below 25°C. Store the vial in the outer packaging to protect it from light. Do not freeze.

For single use only.

Physical and chemical stability has been demonstrated under the conditions of use 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 in-use storage times and conditions before use are the responsibility of the user and normally should not exceed 24 hours between 2 and 8°C, unless the handling has been carried out in controlled and validated aseptic conditions.

This medicine is a clear and colorless solution, practically free from visible particles. The solution should not be used if it has a slightly yellow or pink or brown color, or if it contains particles or a precipitate.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the pack and other information

Composition of Vipranop

• The active substance is noradrenaline (norepinephrine) (as noradrenaline (norepinephrine) tartrate).

Each ml of solution contains 5 micrograms of noradrenaline (norepinephrine), equivalent to 10 micrograms of noradrenaline (norepinephrine) tartrate.

Each 20 ml vial contains 100 micrograms of noradrenaline (norepinephrine), equivalent to 200 micrograms of noradrenaline (norepinephrine) tartrate.

Each 50 ml vial contains 250 micrograms of noradrenaline (norepinephrine), equivalent to 500 micrograms of noradrenaline (norepinephrine) tartrate.

• The other ingredients are: sodium chloride, disodium edetate, hydrochloric acid (for pH adjustment) and water for injections.

Appearance of Vipranop and pack contents

This medicine is a clear and colorless solution for injection and intravenous infusion, practically free from visible particles, in a 20 ml or 50 ml glass vial closed with a chlorobutyl rubber stopper and an aluminum seal.

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

For further information about this medicine, contact the local representative of the marketing authorisation holder:

Aguettant Ibérica SL

Baldiri Reixac, 4-8, Torre I, 4º

08028 Barcelona

Date of last revision of this leaflet 11/2021.

Other sources of information

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/)

This information is intended only for healthcare professionals:

Quantitative and qualitative composition:

Each ml of solution for injection and infusion contains 10 micrograms of noradrenaline (norepinephrine) tartrate monohydrate, equivalent to 5 micrograms of noradrenaline (norepinephrine) anhydrous.

Each 20 ml vial contains 200 micrograms of noradrenaline (norepinephrine) tartrate monohydrate, equivalent to 100 micrograms of noradrenaline (norepinephrine) anhydrous.

Each 50 ml vial contains 500 micrograms of noradrenaline (norepinephrine) tartrate monohydrate, equivalent to 250 micrograms of noradrenaline (norepinephrine) anhydrous.

Therapeutic indications:

Vipranop 5 micrograms/ml solution for injection and infusion is indicated for the restoration and maintenance of perioperative blood pressure after hypotension induced by spinal or general anesthesia in adults.

Posology:

This presentation is suitable in a perioperative setting, the concentration is not suitable in a critical care setting.

Infusion may be administered as an intravenous bolus via a peripheral venous line or continuous infusion via a syringe pump or infusion pump or intravenous drip chamber.

This medicine should not be diluted before use: it is ready to be used and should not be mixed with other medicines.

The patient should be carefully monitored and should not be left unattended while noradrenaline is being administered.

Care should be taken to avoid extravasation. To prevent shedding and necrosis in areas where extravasation has occurred, the area should be infiltrated as soon as possible with 10 ml to 15 ml of saline solution containing 5 mg to 10 mg of phentolamine. Noradrenaline infusion should be stopped.

Initial rate

The initial infusion dose is between 0.02 µg/kg/min and 0.05 µg/kg/min of noradrenaline (equivalent to 0.04 µg/kg/min and 0.1 µg/kg/min of noradrenaline tartrate). An initial loading dose (intravenous bolus) of 5 µg to 10 µg of noradrenaline (10 µg to 20 µg of noradrenaline tartrate) may be administered before starting the infusion, after spinal anesthesia or induction of general anesthesia.

Dose adjustment

Once noradrenaline infusion is started, the dose may be increased or decreased to maintain adequate blood pressure during the perioperative period. The dose should be adjusted according to the patient's age, weight and clinical condition.

An intravenous bolus of 5 µg to 10 µg of noradrenaline (10 µg to 20 µg of noradrenaline tartrate) may be administered if it is necessary to rapidly increase blood pressure.

Duration of treatment and monitoring

Noradrenaline should be maintained throughout the perioperative period as long as necessary to maintain adequate blood pressure and tissue perfusion.

Discontinuation of therapy

Infusions should be gradually reduced, and abrupt interruption should be avoided, which could result in acute hypotension.

Elderly patients

In general, caution should be exercised when selecting the dose for an elderly patient, starting with the lowest dose in the dosage range, to reflect the increased frequency of decreased hepatic, renal or cardiac function and concomitant disease or other drug therapy.

Refer to the Summary of Product Characteristics for full information on indication and use.