Package leaflet: Information for the user

VasoKINOX, 800 ppm mol/mol, medicinal gas, compressed
Nitric oxide
Please read this leaflet carefully before using this medicine, as it contains
important information for the user.

Keep this leaflet, as you may need to read it again.
If you have any further questions, please consult your doctor.
If you experience any side effects, including any possible side effects not listed in this leaflet, tell your doctor.

Leaflet contents:

What VasoKINOX, 800 ppm mol/mol, compressed medicinal gas is and what it is used for
Important information before using VasoKINOX, 800 ppm mol/mol, compressed medicinal gas
How to use VasoKINOX, 800 ppm mol/mol, compressed medicinal gas
Possible side effects
How to store VasoKINOX, 800 ppm mol/mol, compressed medicinal gas
Contents of the pack and other information

1. What VasoKINOX is and what it is used for
VasoKINOX is a gas mixture consisting of nitric oxide and nitrogen, used

for the treatment of newborns with pulmonary insufficiency associated with increased pulmonary vascular pressure
for the treatment of acute pulmonary hypertension (increased blood pressure in the pulmonary circulation) that may occur during cardiac surgery in adults and children and adolescents aged 0–17 years.

2. Important information before using VasoKINOX

Do not use VasoKINOX:

if there is hypersensitivity to nitric oxide,
in newborns with certain heart defects, such as abnormal circulation within the heart (right-to-left shunt or "malignant" left-to-right shunt associated with a persistent ductus arteriosus).

Warnings and precautions

Do not discontinue treatment with VasoKINOX abruptly.
Blood samples will be taken before starting treatment and regularly during therapy to monitor certain parameters.

Other medicines and VasoKINOX
Inform your doctor about all medicines currently used or recently used,
as well as any medicines the patient intends to take.

Exercise caution when administering VasoKINOX if the following medicines are used concomitantly:
“nitric oxide donors” (such as sodium nitroprusside and nitroglycerin). Their effects may be additive to those of VasoKINOX.
medicines that increase methemoglobin concentration in blood, such as alkyl nitrates and sulfonamides, prilocaine.
prostacyclin and its analogues
- Inform the doctor about all recently taken medicines.
- The decision on whether simultaneous treatment with VasoKINOX and another medicine is necessary lies with the doctor.

Pregnancy, breastfeeding and fertility:
Pregnancy: The effect of using VasoKINOX in pregnant women is unknown. As a precautionary measure, the use of VasoKINOX during pregnancy is not recommended.
Breastfeeding: It is not known whether nitric oxide/metabolites pass into human milk. A decision whether to discontinue breastfeeding or discontinue treatment with VasoKINOX should be made after considering the benefits of breastfeeding for the child and the benefits of treatment with VasoKINOX for the mother.
Fertility: No studies on the effect on fertility have been conducted. If you are pregnant or breastfeeding, suspect you may be pregnant, or are planning to become pregnant, consult your doctor before using this medicine.

3. How to use VasoKINOX

VasoKINOX is a medical gas administered exclusively in hospitals by medical personnel.
The physician will determine the appropriate dose of VasoKINOX, as well as the duration of treatment, depending on the patient's clinical condition and age.
VasoKINOX is administered by inhalation using mechanical ventilation, after dilution with an air/oxygen mixture, to patients in intensive care units requiring assisted respiration, as well as in the operating room.
Upon contact with oxygen, nitric oxide may be converted into nitrogen dioxide, which may irritate the bronchi. Therefore, during therapy, the inhaled concentrations of nitric oxide and nitrogen dioxide are continuously monitored.
In certain clinical situations, administration of nitric oxide via mask may be possible for a very short period (5 to 10 minutes). If more VasoKINOX has been administered than recommended: The physician will take appropriate corrective measures. Discontinuation of VasoKINOX: At the end of treatment in the intensive care unit, the physician will gradually reduce the dose of VasoKINOX (tapering-off phase), monitoring changes in the patient's condition. In practice, abrupt discontinuation of therapy after several hours of administration may lead to worsening of the patient's clinical status, known as the "rebound effect". For any additional questions regarding the use of this medicine, please consult the physician for further information.

4. Possible adverse reactions

Like all medicines, VasoKINOX can cause adverse reactions, although not everyone experiences them.

Very common adverse reactions (affecting more than 1 in 10 people) associated with VasoKINOX therapy include:

Low platelet count.

Common adverse reactions (affecting more than 1 in 100 people) associated with VasoKINOX therapy include:

Low blood pressure, reduced lung air volume, or lung collapse.

Uncommon adverse reactions (occurring in more than 1 in 1,000 people but less than 1 in 100) include:

Increased methemoglobin levels (a form of hemoglobin unable to carry oxygen), which reduces oxygen release to body tissues.

Adverse reactions for which the frequency is unknown (frequency cannot be estimated from available data) include:

Bradycardia (slowed heart rate) or low blood oxygen levels (hypoxemia) resulting from sudden discontinuation of treatment,
Headache, dizziness, sore throat, and shortness of breath following accidental exposure to nitric oxide (e.g., due to leakage from equipment or cylinders). If headache or other symptoms occur in a child or patient receiving VasoKINOX, personnel must be informed immediately.

Reporting of adverse reactions

If any adverse reactions occur, including those not listed in this leaflet, inform your doctor, pharmacist, or nurse. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions, Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw, tel.: +48 22 49 21 301, fax: +48 22 49 21 309, e-mail: [email protected]. Adverse reactions can also be reported via the responsible subject. Reporting adverse reactions helps increase the knowledge on the safety of this medicinal product.

5. How to store the medicine VasoKINOX

Storage of the VasoKINOX cylinder is ensured by the hospital.
Keep out of the reach and sight of children.
Protect the cylinder from damage or falling and keep away from flammable substances and combustible materials, as well as moisture. There are no special requirements regarding storage temperature of the medicine.
Securely fasten the cylinders to maintain them in an upright position and store them in a properly ventilated area.
Do not use this medicine after the expiry date stated on the label of the batch.
Do not dispose of the cylinder after emptying. Empty cylinders will be collected by the supplier.

6. Contents of the packaging and other information

What VasoKINOX contains

The active substance is nitric oxide, at a dose of 800 ppm mol/mol.
The other component is nitrogen.

What VasoKINOX looks like and contents of the container
Cylinder of 2 L or 11 L capacity. Aluminium alloy cylinder equipped with a residual pressure valve made of stainless steel and a specific connector for the socket. Cylinder body white, Turkish blue cup.

A 2-litre cylinder filled to 200 bar delivers 0.4 m³ of gas at 1 bar pressure and a temperature of 15°C.
An 11-litre cylinder filled to 200 bar delivers 2.1 m³ of gas at 1 bar pressure and a temperature of 15°C.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Air Liquide Santé International
75 Quai D’orsay
75007 Paris
France

Manufacturer
Air Liquide Santé France
“Les Petits Carreaux”
2, Avenue Du Lys
94380 Bonneuil-Sur-Marne
France

Marketing Authorisation Number
This medicinal product is authorised in the European Economic Area countries under the following names:

Austria: VasoKINOX
Belgium: VasoKINOX
Denmark: Vasokinox
Germany: VasoKINOX
Italy: VasoKINOX
Luxembourg: VasoKINOX
Norway: Vasokinox
Poland: VasoKINOX
Portugal: VasoKINOX
Spain: VasoKINOX
Sweden: Vasokinox
Netherlands: VasoKINOX

Prescription and supply conditions: Rpz - Medicinal product supplied on prescription only.

The following information is intended exclusively for healthcare professionals:

To avoid accidents, the following instructions must be strictly observed:

Check whether the device is ready for operation before use.
Securely fasten cylinders to the rack using chains and hooks to prevent accidental falling.
Never open the valve abruptly: slowly open the valve counterclockwise to the end, then turn it back a quarter turn clockwise.
Never handle a cylinder whose valve is not protected by a safety cap and protective seal.
Use a specific ISO 5145 (2004) connector: No. 29 designated for NO/N₂ (100 ppm < NO < 1000 ppm) W30x2 15.2–20.8 DR.
Use a pressure regulator capable of withstanding a pressure of at least 1.5 times the maximum working pressure of the gas cylinder (200 bar).
Before each new use, purge the pressure reducer/flowmeter using a nitric oxide/nitrogen mixture.
Do not attempt to repair a defective valve.
Do not tighten the pressure reducer/flowmeter with pliers, as this may crush the gasket and damage the delivery device.
Vent exhaled gases outdoors (avoiding areas where gases could accumulate). Before use, ensure that the room is equipped with an adequate ventilation system to remove gases in case of malfunction or accidental leakage.
Since nitric oxide is colorless and odorless, the use of a detection system is recommended in all rooms where nitric oxide will be used or stored.
The American (NIOSH) and European occupational safety and health authorities recommend the following exposure limit values:
- NO: 25 ppm over 8 hours (30 mg/m³)
- NO₂: 2 ppm (4 mg/m³)
To comply with the above recommendations, analysis of nitric oxide and nitrogen dioxide concentrations in the atmosphere must be performed.
Installation of a permanent pipeline system for nitric oxide, including a station with reserve gas cylinders, a fixed network, and inhalation units, is prohibited.