VASOKINOX 800 PPM GAS COMPRESSED MEDICINAL

Introduction

Package Leaflet: Information for the User

VasoKINOX 800 ppm mol/mol, medicinal compressed gas

Nitric oxide

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 further questions, ask your doctor or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you experience any side effects, talk to your doctor or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the package leaflet

1. What is VasoKINOX 800 ppm mol/mol, medicinal compressed gas and what is it used for
2. What you need to know before you start using VasoKINOX 800 ppm mol/mol, medicinal compressed gas
3. How to use VasoKINOX 800 ppm mol/mol, medicinal compressed gas
4. Possible side effects
5. Storage of VasoKINOX 800 ppm mol/mol medicinal compressed gas
6. Contents of the pack and further information

1. What is VasoKINOX and what is it used for

VasoKINOX is a gas mixture, composed of nitric oxide and nitrogen, used for

treatment of newborns with pulmonary insufficiencyassociated with increased blood pressure in the pulmonary circulation

treatment of acute pulmonary hypertension(increased blood pressure in the pulmonary circulation) that may occur during cardiac surgery in adults, children, and adolescents, from 0 to 17 years.

2. What you need to know before you start using VasoKINOX

Do not use VasoKINOX:

• if you are hypersensitive to nitric oxide
• in neonates with certain heart problems, such as abnormal circulation within the heart (right-to-left shunt, or left-to-right "malignant" arterial canal

Warnings and precautions

Talk to your doctor or nurse before you start using VasoKINOX.

• Treatment with VasoKINOX should not be stopped abruptly.
• Blood samples are taken before treatment and regularly during administration to monitor certain parameters.
• There have been reports of fluid retention in the lungs with nitric oxide in patients with a disease caused by a blocked or narrow vein in the lungs. If you (as a patient) or your child (as a patient) experience shortness of breath or difficulty breathing, contact your doctor immediately.

Using VasoKINOX with other medicines

Tell your doctor if you are using, have recently used, or might use any other medicines.

• VasoKINOX should be used with caution if the following medicines are taken at the same time:

• "Nitric oxide donors" (such as medicines containing sodium nitroprusside and nitroglycerin). Their effect may be added to that of VasoKINOX.
• Medicines that can increase the concentration of methemoglobin in the blood, such as those containing nitrate alkaloids and sulfonamides, prilocaine.
• Prostacyclin and its analogs
  • It is up to the doctor to decide whether it is necessary to treat you with VasoKINOX and other medicines at the same time.

Pregnancy, breastfeeding, and fertility:

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor before using this medicine.

Pregnancy:

The effect of administering VasoKINOX in pregnant women is unknown. As a precautionary measure, it is preferable to avoid using VasoKINOX during pregnancy.

Breastfeeding:

It is unknown whether nitric oxide/metabolites are excreted in human milk.

A decision must be made whether to discontinue breastfeeding or discontinue therapy with VasoKINOX, taking into account the benefits of breastfeeding for the child and the benefits of therapy for the woman.

Fertility:

No fertility studies have been conducted.

3. How to use VasoKINOX

Follow exactly the administration instructions of this medicine indicated by your doctor. In case of doubt, consult your doctor again.

• VasoKINOX is a medicinal gas administered only in hospitals by healthcare professionals.
• The doctor will determine the appropriate doseof VasoKINOX, as well as the duration of treatment, depending on your clinical condition and age.
• VasoKINOX is administered by inhalation, through mechanical ventilationafter dilution in an air/oxygen mixture to patients in intensive care units with respiratory support and also in the operating room.
• When in contact with oxygen, nitric oxide can be converted into nitrogen dioxide, which irritates the bronchi. For this reason, during its administration, the inhaled concentrations of nitric oxide and nitrogen dioxide are constantly measured.
• Under certain clinical circumstances, it is possible to administer nitric oxide through ventilation with a maskfor a very short period (5 to 10 minutes).

If you use more VasoKINOX than you should:Your doctor will take the necessary measures

If you stop using VasoKINOX:

At the end of treatment in intensive care, the doctor will gradually reduce the dose of VasoKINOX administered (withdrawal phase), monitoring the change in your condition.

In fact, abrupt interruption of treatment after several hours of administration can cause a worsening of the clinical condition: this is what is called a "rebound effect".

If you have any other questions about 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.

Very common side effects (affect more than 1 in 10 people) in association with VasoKINOX therapies include:

. Low platelet count in the blood

Common side effects (affect more than 1 in 100 people) in association with VasoKINOX therapies include:

. Low blood pressure, lack of air, or pulmonary collapse.

Uncommon side effects (affect between 1 in 100 and 1 in 1,000 people) are:

. Increased amount of methemoglobin (a form of hemoglobin that cannot carry oxygen) that reduces the amount of oxygen released in the tissues.

Side effects that may occur but whose frequency is unknown (frequency cannot be estimated from the available data) are:

. Bradycardia (slow heart rate) or too low oxygen levels in the blood (oxygen desaturation/hypoxemia) due to abrupt interruption of treatment

. Headache, dizziness, dry throat, or shortness of breath after accidental exposure to nitric oxide (e.g., equipment leak or balloon)

You should inform the staff directly if you experience a headache while you are near your child during treatment with VasoKINOX

Reporting of side effects:

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

5. Storage of VasoKINOX

• Keep this medicine out of the sight and reach of children.
• Do not use this medicine after the expiry date stated on the label.
• This medicine does not require special temperature conditions for storage.
• The storage of VasoKINOX cylinders is carried out in the hospital.
• The cylinder must be protected to avoid breakage and falls and must be kept away from any flammable or combustible material and humidity.
• The cylinders must be kept in a vertical position and well secured and stored in a well-ventilated area.

• When the gas cylinder is empty, do not dispose of it. The empty cylinders will be collected by the supplier.

6. Contents of the pack and further information

Composition of VasoKINOX

• The active substance is nitric oxide; its dose is 800 ppm mol/mol
• The other components are nitrogen

Appearance of the product and contents of the pack

A 2-liter cylinder filled to 200 bar provides 0.4 m3 of gas at a pressure of 1 bar at 15°C.

A 11-liter cylinder filled to 200 bar provides 2.1 m3 of gas at a pressure of 1 bar at 15°C

Marketing authorization holder and manufacturer

Marketing authorization holder

AIR LIQUIDE SantéINTERNATIONAL

75 Quai d’Orsay

75007 PARIS Cedex 07

FRANCE

Manufacturer

AIR LIQUIDE SantéFRANCE

“Les Petits Carreaux”

2, avenue du Lys

94380 BONNEUIL-SUR-MARNE

FRANCE

This medicine has been authorized in the EEA Member States with the following names:

• Austria: VasoKINOX
• Belgium: VasoKINOX
• Denmark: VasoKINOX
• Germany: VasoKINOX
• Italy: VasoKINOX
• Luxembourg: VasoKINOX
• Norway: Vasokinox
• Poland: VasoKINOX
• Portugal: VasoKINOX- Spain: VasoKINOX
• Switzerland: Vasokinox- Netherlands: VasoKINOX

Date of last revision of this leaflet: May 2025

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

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This information is intended only for healthcare professionals:

To avoid any incidents, the following instructions must be strictly followed:

. Check that the equipment is in good condition before use

. Securely fasten the cylinders using chains or hooks in the basket to avoid accidental falls

. Never open a valve abruptly: open to the left, slowly and completely, then turn the valve a quarter turn

. Do not handle a cylinder whose valve is not protected by a tulip or protection system

. Use a specific ISO 5245 (2004) connector: No. 29 specific NO/N2 (100 ppm

. A pressure regulator that can withstand a pressure at least equal to 1.5 times the maximum operating pressure (200 bar) of the gas cylinder must be used

. For each new use, purge the pressure reducer/flow meter using a nitric oxide/nitrogen mixture

. Do not attempt to repair a faulty valve

. Do not tighten the pressure reducer/flow meter using a clamp, as this may damage the seal and the administration device

. Evacuate exhaled gases to the outside (avoiding areas where they can accumulate). Before use, it must be ensured that the room has an adequate ventilation system for gas evacuation in case of an accident or accidental leaks

. Since nitric oxide is colorless and odorless, the use of a detection system is recommended in all rooms where it will be used or stored

. European reference agencies responsible for occupational safety and health recommend the following exposure limits for medical personnel during 8 hours:

• NO: 2 ppm (2.5 mg/m3)
• NO2: 0.5 ppm (0.96 mg/m3)

To comply with the above recommendations, an analysis of nitric oxide and nitrogen dioxide in the atmosphere must be implemented.

. The installation of a nitric oxide piping system with a gas cylinder supply source, fixed network, and terminal units is prohibited.