Label: information for the user

VasoKINOX450 ppm mol/mol, medicinal compressed gas

Nitric oxide

Read this label carefully before starting to take this medication because it contains important information for you

• Keep this label, as you may need to read it again.
• If you have any questions, consult your doctor.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are not listed in this label.

1. What is VasoKINOX 450 ppm mol/mol, medicinal compressed gas and how is it used

2. What you need to know before starting to use VasoKINOX 450 ppm mol/mol, medicinal compressed gas

3. How to use VasoKINOX 450 ppm mol/mol, medicinal compressed gas

4. Possible adverse effects

5. Storage of VasoKINOX 450 ppm mol/mol medicinal compressed gas

6. Contents of the package and additional information

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

. the treatmentof newborns with pulmonary insufficiencyassociated with an increase in blood pressure in the pulmonary circulation

. the treatment of acute pulmonary hypertension(increase in blood pressure in the pulmonary circulation) that may occurduring cardiac surgeries in adults and neonates, infants, small children, children and adolescents, from 0 to 17 years

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 derivation, or with a "malignant" right-left arterial canal)

Warnings and precautions

• Treatment with VasoKINOX should not be stopped abruptly.
• Blood samples are taken before treatment and regularly during administration to monitor certain parameters.

Use of VasoKINOX with other medications

• VasoKINOX should be administered with caution if the following medications are taken at the same time:
• • "Nitric oxide donors" (such as medications containing sodium nitroprusside and nitroglycerin). Their effect may add to that of VasoKINOX.
  • Medications that generate methemoglobin (such as medications containing nitrates, alkaloids, and sulfamides, prilocaine). They may increase the concentration of methemoglobin in the blood.
  • Prostacyclin and its analogs

• Inform your doctor if you are taking or have taken any other medication recently.

• It is the doctor who will decide whether it is necessary to treat you with VasoKINOX and with other medications at the same time.

Pregnancy, breastfeeding, and fertility

Pregnancy

The effect of administering VasoKINOX to pregnant women is unknown.

As a precaution, it is recommended to avoid using VasoKINOX during pregnancy.

Breastfeeding:

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

A decision should be made about whether to interrupt breastfeeding or interrupt VasoKINOX therapy, taking into account the benefits of breastfeeding for the child and the benefits of therapy for the woman.

Fertility

No studies have been conducted on fertility.

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

• VasoKINOX is a medicinal gasadministered exclusively in hospitals by healthcare professionals.

• The doctor will determine the appropriate doseof VasoKINOX,as well as the duration of treatment, depending on their clinical condition and age.

• VasoKINOX is administered byinhalation, via mechanical ventilationafter dilution in a mixture of air/oxygen to patients in intensive care units with respiratory support and also in the operating room.

• In contact with oxygen, nitric oxide can convert to nitrogen dioxide, which irritates the bronchi. For this reason, during administration, the inhaled concentrations of nitric oxide and nitrogen dioxide are constantly measured.

• In certain clinical circumstances, it is possible to administer nitric oxide via ventilationwith a maskfor a very short period of time (5 to 10 minutes).

Ifyou have been administeredmoreVasoKINOXthanyou should have:

Your doctor will take the necessary measures.

Ifthe treatment ofVasoKINOX is interrupted:

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

Indeed, a sudden interruption of treatment after several hours of administration can cause a deterioration of the clinical condition: this is what is called a "rebound effect".

If you have any other questions about the use of this medication, consult your doctor for more information.

Like all medications,VasoKINOXmay cause adverse effects, although not everyone will experience them.

Very common adverse effects (affect more than 1 in 10 patients) associated with VasoKINOX therapy include:

. Low platelet count in the blood.

Common adverse effects (affect more than 1 in 100 patients) associated with VasoKINOX therapy include:

. Low blood pressure, without air or pulmonary collapse.

Adverse effects that may occur, but with low frequency (affect between 1 in 100 and 1 in 1000 patients) are:

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

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

. Bradycardia (low heart rate) or low oxygen levels in the blood (hypoxemia) due to a sudden interruption of treatment

. Headache, dizziness, dry throat, or shortness of breath after accidental exposure to nitric oxide (for example, a leak from equipment or a bullet)

You must inform the staff directly if you experience a headache while near your child during VasoKINOX treatment)

Reporting Adverse Effects:

If you experience any type of adverse effect, consult your doctor or pharmacist. Even if it is a possible adverse effect that does not appear in this prospectus. You can also report them directly through the Spanish System for Pharmacovigilance of Medicines for Human Use:http://.www.notificaRAM.es. By reporting adverse effects, you can contribute to providing more information about the safety of this medication.

• This medication does not require special temperature conditions for storage.
• VasoKINOX balls are stored in the hospital.
• Keep this medication out of the sight and reach of children.
• The ball must be protected to prevent breakage and falls and must be kept away from any flammable or combustible materials and moisture.
• The balls must be kept in an upright position and securely fastened and must be stored in a well-ventilated area.
• Do not use this medication after the expiration date that appears on the label of the lot.

When the gas cartridge is empty, do not dispose of it. Empty cartridges will be collected by the supplier.

Composition ofVasoKINOX

-The active principle is nitric oxide; its dose is 450 ppm mol/mol

• The other component is nitrogen

Appearance of the product and contents of the container

A 5-liter cartridge filled to 200 bar provides 0.94 m3of gas at a pressure of 1 bar at15°C.

A 11-liter cartridge filled to 200 bar provides 2.1 m3of gas at a pressure of 1 bar at15°C.

A 20-liter cartridge filled to 200 bar provides 3.8 m3of gas at a pressure of 1 bar at15°C.

Holder of the marketing authorization and manufacturer

Holder of the marketing authorization

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

Marketing authorization number

69773

This medicinal product has been authorized in the Member States of the EEA with the following names:

• Austria: VasoKINOX 450 ppm mol/mol Gas zur medizinischen Anwendung, druckverdichet
• Belgium: VasoKINOX
• Denmark: VasoKINOX
• Germany: VasoKINOX 450 ppm (mol/mol), Gas zur medizinischen Anwendung, druckverdichtet
• Italy: VasoKINOX
• Luxembourg: VasoKINOX
• Norway: Vasokinox
• Poland: VasoKINOX
• Portugal: VasoKINOX
• Spain: VasoKINOX
• Switzerland: Vasokinox
• Netherlands: VasoKINOX

Prescription and dispensing conditions:

Subject to medical prescription

Last review date of this leaflet: November 2017

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The following information is intended for healthcare professionals:

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

. check that the equipment is in good condition before use

. ensure the cartridges are securely fastened using chains or hooks in the basket to prevent accidental falls

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

. do not take a cartridge where the valve is not protected by a tulip or a protection system

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

. a pressure regulator that can admit a pressure at least equal to 1.5 the maximum operating pressure (200 bar) of the gas cartridge must be used

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

. do not attempt to repair a faulty valve

. do not tighten the pressure-reducer / flow-meter using a pair of pliers, otherwise the seal may be damaged and the administration device may be damaged

. evacuate the exhaled gases to the outside (avoiding areas where they may accumulate). Before use, ensure that the room has an adequate ventilation system for the evacuation of gases in case of an accident or accidental leaks

. as nitric oxide is colourless and odourless, it is recommended to use a detection system in all rooms where it is to be used or stored

. the American (NIOSH) and European agencies responsible for safety and health at work recommend the following exposure limits for medical staff:

• NO: 25 ppm for 8 hours (30 mg/m3)
• NO2: 2 ppm ( 4 mg/m3)

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

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

The detailed and updated information on this medicinal product is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS) http://www.aemps.gob.es