Vasokinox

Package leaflet: Information for the user

VasoKINOX 450 ppm mole/mole, medicinal gas, compressed

Nitric oxide
Please read this leaflet carefully before using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, consult your doctor.
• If you experience any side effects, including those not listed in this leaflet, consult your doctor.

Contents of this leaflet

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

1. What VasoKINOX is and what it is used for

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

• treating newborns with respiratory failure associated with increased blood pressure in the pulmonary circulation;
• treating acute pulmonary hypertension (increased blood pressure in the pulmonary circulation) that may occur during cardiac surgery in adults and in newborns, infants, children, and adolescents aged 0 to 17 years.

2. What you need to know before using VasoKINOX

Do not use VasoKINOX

• If you are hypersensitive to nitric oxide.
• In newborns with certain cardiac dysfunctions, such as abnormal blood circulation within the heart (right-to-left shunt or left-to-right malignant ductus arteriosus).

Warnings and precautions

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

Other medicines and VasoKINOX

• VasoKINOX must be administered with caution when used concomitantly with the following medicines:
• "Nitric oxide donors" (such as medicines containing sodium nitroprusside and nitroglycerin). Their effects may add up to those of VasoKINOX.
• Medicines that may cause methaemoglobinaemia (such as medicines containing alkyl nitrates and sulfonamides, prilocaine). These may increase blood methaemoglobin concentration.
• Prostacyclin and its analogues.
• Inform your doctor if you are taking, or have recently taken, any other medicines.
• It is the doctor who decides whether treatment with VasoKINOX and other medicines at the same time is necessary.

Pregnancy, breastfeeding and fertility
Pregnancy
The effect of VasoKINOX administration in pregnant women is unknown.
As a precautionary measure, it is preferable to avoid using VasoKINOX during pregnancy.
Breastfeeding
It is not known whether nitric oxide/metabolites are excreted in breast milk.
A decision must be made whether to discontinue breastfeeding or to discontinue therapy with VasoKINOX, taking into account the benefit of breastfeeding for the child and the benefit of therapy for the woman.
Fertility
No fertility studies have been conducted.
If you are pregnant, suspect you may be pregnant, are planning a pregnancy, or are breastfeeding with breast milk, consult your doctor before taking this medicine.

3. How to use VasoKINOX

• VasoKINOX is a medicinal gas administered only in hospitals by healthcare professionals.
• Your doctor will determine the appropriate dose of VasoKINOX and the duration of treatment, based on your clinical condition and age.
• VasoKINOX is administered by inhalation, via mechanical ventilation, after dilution in an air/oxygen mixture, to patients receiving assisted breathing who are hospitalized in intensive care units and operating rooms.
• Upon contact with oxygen, nitric oxide may be converted into nitrogen dioxide, which is an irritant to the bronchi. For this reason, during administration, the concentrations of inhaled nitric oxide and nitrogen dioxide are continuously monitored.
• In certain clinical circumstances, administration of nitric oxide via ventilation using a mask may be possible for a very short duration (from 5 to 10 minutes).

If you are given more VasoKINOX than you should receive
Your doctor will take appropriate measures.
If you stop treatment with VasoKINOX
At the end of intensive care treatment, your doctor will gradually reduce the dose of VasoKINOX administered (weaning phase), monitoring changes in your condition.
Indeed, sudden interruption of treatment after many hours of administration may result in worsening of your clinical status: this is known as the "rebound effect".
For any further questions about the use of this medicine, please ask your doctor for more information.
If you have any doubts about how to use VasoKINOX, consult your doctor.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Very common side effects (occurring in more than 1 in 10 patients) observed during treatment with
VasoKINOX include:

• Low platelet count.

Common side effects (occurring in more than 1 in 100 patients) observed during treatment with
VasoKINOX include:

• Low blood pressure, hypoxic lung or collapsed lung.

Side effects observed but not common (occurring between 1 in 100 and 1 in 1000 patients) are:

• Increase in methaemoglobin (a form of haemoglobin unable to carry oxygen), leading to reduced oxygen delivery to tissues.
  Side effects observed but with unknown frequency (frequency cannot be estimated from the available data) are:
• Bradycardia (slow heart rate) or too low oxygen levels in the blood (oxygen desaturation/hypoxaemia) due to sudden interruption of treatment.
• Headache, dizziness, dry throat or shortness of breath following accidental exposure to nitric oxide (e.g.: leaks from the device or cylinder). Please inform medical staff immediately if you experience headache when near your child or a patient receiving VasoKINOX therapy.

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, talk to your doctor.
You can also report side effects directly via the national reporting system at www.agenziafarmaco.gov.it/it/responsabili. Reporting side effects helps provide more information on the safety of this medicine.

5 How to store VasoKINOX

• Storage of VasoKINOX cylinders is the responsibility of the hospital.
• Keep this medicine out of the sight and reach of children.
• The cylinder must be protected to prevent breakage or falling and must be kept away from flammable or combustible materials and moisture, at a temperature between -10°C and +50°C.
• Cylinders must be secured to remain in an upright position and stored in a well-ventilated area.
• Do not use this medicine after the expiry date stated on the label.
• When the gas cylinder is empty, do not dispose of it in household waste. Empty gas cylinders will be collected by the supplier.

6. Package contents and other information

What VasoKINOX contains

• The active substance is nitrogen oxide; its dosage is 450 ppm mole/mole.
• The excipient is nitrogen.

Description of the appearance of VasoKINOX and contents of the pack
A 5-litre cylinder filled to 200 bar delivers 0.94 m³ of gas at a pressure of 1 bar and 15°C.
An 11-litre cylinder filled to 200 bar delivers 2.1 m³ of gas at a pressure of 1 bar and 15°C.
A 20-litre cylinder filled to 200 bar delivers 3.8 m³ of gas at a pressure of 1 bar and 15°C.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
AIR LIQUIDE S*anté* INTERNATIONAL
75 Quai d’Orsay
75341 PARIS Cedex 07
FRANCE

Manufacturer
AIR LIQUIDE S*anté* FRANCE
“Les Petits Carreaux”
2, avenue du Lys
94380 BONNEUIL-SUR-MARNE
FRANCE

This medicinal product is authorised in the Member States of the European Economic Area under the following names:

• Austria: VasoKINOX 450 ppm mol/mol Gas zur medizinischen Anwendung, druckverdichtet
• 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
• Sweden: VasoKINOX
• Netherlands: VasoKINOX

This leaflet was last updated on

The following information is intended for healthcare professionals only:

To prevent any accidents, strictly follow the instructions listed below:

• check that the equipment is in good condition before use;
• securely fasten cylinders with chains or locks on the cylinder rack to prevent accidental falls;
• never open the valve abruptly: open it slowly and fully by turning counterclockwise, then turn the valve one-quarter turn clockwise;
• do not handle a cylinder whose valve lacks the protective cap and cover;
• use a specific connector compliant with ISO 5145 (2004) standards: No. 29 specific for NO/N₂ (100 ppm < NO < 1000 ppm) W30x2 15.2-20.8 DR;
• a pressure regulator must be used that allows at least 1.5 times the maximum working pressure (200 bar) of the gas cylinder;
• at each new use, purge the flowmeter/pressure reducer using the nitric oxide/nitrogen mixture;
• do not attempt to repair a defective valve;
• do not tighten the pressure reducer/flowmeter with pliers, as this may damage the sealing gasket and consequently damage the delivery device;
• exhaust exhaled gases to the outside (avoiding areas where gases could accumulate). Before use, verify that the room has an adequate ventilation system for gases in case of accidents or accidental leaks;
• since nitric oxide is colorless and odorless, it is recommended to use a detection system in all rooms where nitric oxide is used or stored;
• American (NIOSH) and European agencies responsible for occupational safety and health recommend the following exposure limits for medical personnel:
  • NO: 25 ppm for 8 hours (30 mg/m³)
  • NO₂: 2 ppm (4 mg/m³)

To comply with the above recommendations, an analysis of nitric oxide and nitrogen dioxide concentrations in the atmosphere must be performed.
It is prohibited to construct a nitric oxide pipeline distribution system that includes a cylinder station (central plant), fixed piping network, and terminal units at the patient's bedside.

Package leaflet: Information for the user

VasoKINOX 800 ppm mole/mole, medicinal gas, compressed

Nitric oxide
Please read this leaflet carefully before using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, consult your doctor.
• If you experience any adverse reaction, including those not listed in this leaflet, contact your doctor.

Contents of this leaflet:

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

1. What VasoKINOX is and what it is used for

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

• treating newborns with respiratory failure associated with increased blood pressure in the pulmonary circulation
• treating acute pulmonary hypertension ( increased blood pressure in the pulmonary circulation ) that may occur during cardiac surgery in adults, children and adolescents aged 0 to 17 years .

2. What you need to know before using VasoKINOX

Do not use VasoKINOX:

• If you are hypersensitive to nitric oxide.
• In newborns with certain cardiac dysfunctions, such as abnormal blood circulation within the heart (right-to-left shunt or left-to-right malignant ductus arteriosus).

Warnings and precautions:

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

Other medicines and VasoKINOX:
Inform your doctor if you are taking, have recently taken, or might take any other medicine.

• VasoKINOX should be administered with caution when used simultaneously with the following medicines:
• "Nitric oxide donors" (such as medicines containing sodium nitroprusside and nitroglycerin). Their effects may add up to those of VasoKINOX.
• Medicines that may cause methaemoglobinaemia (such as medicines containing alkyl nitrates and sulfonamides, prilocaine).
• Prostacyclin and its analogues.
• Inform your doctor if you are taking, have recently taken, or might take any other medicine.
• It is the doctor who decides whether treatment with VasoKINOX and other medicines at the same time is necessary.

Pregnancy, breastfeeding and fertility
Pregnancy:
The effect of VasoKINOX administration in pregnant women is unknown.
As a precautionary measure, it is preferable to avoid using VasoKINOX during pregnancy.
Breastfeeding:
It is not known whether nitric oxide/metabolites are excreted in human milk.
A decision must be made whether to discontinue breastfeeding or to discontinue therapy with VasoKINOX, taking into account the benefit of breastfeeding for the child and the benefit of therapy for the woman.
Fertility:
No fertility studies have been conducted.
If you are pregnant, suspect you may be pregnant, planning to become pregnant, or breastfeeding, consult your doctor before taking this medicine.

3. How to use VasoKINOX

• VasoKINOX is a medicinal gas administered only in hospitals by healthcare professionals.
• The doctor will determine the appropriate dose of VasoKINOX and the duration of treatment, based on your clinical condition and age.
• VasoKINOX is administered by inhalation via mechanical ventilation, after dilution in an air/oxygen mixture, to patients undergoing assisted ventilation and hospitalized in intensive care units and operating rooms.
• Upon contact with oxygen, nitric oxide may be converted into nitrogen dioxide, which is an irritant agent for the bronchi. For this reason, during administration, the concentrations of inhaled nitric oxide and nitrogen dioxide are continuously monitored.
• In certain clinical circumstances, nitric oxide administration via ventilation using a mask may be possible for a very short duration (from 5 to 10 minutes).

If you take more VasoKINOX than you should:
The doctor will take appropriate measures.
If you stop treatment with VasoKINOX:
At the end of intensive care treatment, the doctor will gradually reduce the administered dose of VasoKINOX (weaning phase), monitoring changes in your condition.
Indeed, sudden interruption of treatment after many hours of administration may result in worsening of your clinical status: this is known as the "rebound effect".
If you have any doubts about the use of this medicine, consult your doctor.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone experiences them.
Very common side effects (occurring in more than 1 out of 10 patients) associated with VasoKINOX therapy include:

• Low platelet count.

Common side effects (occurring in more than 1 out of 100 patients) associated with VasoKINOX therapy include:

• Low blood pressure, hypoxic lung or collapsed lung.

Side effects observed but not common (occurring in between 1 out of 100 and 1 out of 1000 patients) are:

• Increase in methaemoglobin (a form of haemoglobin unable to carry oxygen), leading to reduced oxygen delivery to tissues.

Side effects observed but with unknown frequency (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 sudden discontinuation of treatment,
• Headache, dizziness, dry throat or shortness of breath following accidental exposure to nitric oxide (e.g. leaks from the device or cylinder).

Please inform the healthcare staff immediately if you experience headache when near your child or a patient receiving VasoKINOX therapy.
Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, talk to your doctor. You may also report side effects directly via the national reporting system at www.aifa.gov.it/content/segnalazioni-reazioni-avverse. Reporting side effects helps provide more information on the safety of this medicine.

5 How to store VasoKINOX

• This medicine does not require any special storage temperature.
• Storage of VasoKINOX cylinders is the responsibility of the hospital.
• Keep this medicine out of the sight and reach of children.
• The cylinder must be protected to prevent breakage or falling and must be kept away from flammable or combustible materials and from moisture.
• Cylinders must be secured to remain in an upright position and must be stored in a well-ventilated area.
• Do not use this medicine after the expiry date stated on the label.
• When the gas cylinder is empty, do not dispose of it yourself. The empty gas cylinder will be collected by the supplier.

6. Package contents and other information

What VasoKINOX contains:

• The active substance is nitrogen oxide, with a dosage of 800 ppm mole/mole.
• The other component is nitrogen.

Description of the appearance of VasoKINOX and contents of the package
A 2-litre cylinder filled to 200 bar delivers 0.4 m³ of gas at a pressure of 1 bar and 15°C.
An 11-litre cylinder filled to 200 bar delivers 2.1 m³ of gas at a pressure of 1 bar and 15°C.

Marketing Authorization Holder and Manufacturer
Marketing Authorization Holder
AIR LIQUIDE Santé INTERNATIONAL
75 Quai d’Orsay
75341 PARIS Cedex 07
FRANCE

Manufacturer
AIR LIQUIDE Santé FRANCE
“Les Petits Carreaux”
2, avenue du Lys
94380 BONNEUIL-SUR-MARNE
FRANCE

This medicinal product is authorized in the Member States of the European Economic Area 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

This leaflet was last updated on

The following information is intended exclusively for healthcare professionals:

To prevent any accidents, strictly adhere to the instructions listed below:

• check that the equipment is in good condition before use;
• securely fasten cylinders with chains or locks in the rack to prevent accidental falls;
• never open the valve abruptly: open it slowly and fully in a counterclockwise direction, then turn the valve one-quarter turn clockwise;
• do not handle a cylinder whose valve lacks the protective cap and protective wrapping;
• use a specific connector compliant with ISO 5145 (2004) standards: n°29 specific for NO/N₂ (100 ppm < NO < 1000 ppm) W30x2 15.2-20.8 DR;
• a pressure regulator must be used that allows a pressure at least equal to 1.5 times the maximum operating pressure (200 bar) of the gas cylinder;
• at each new use, purge the flowmeter/pressure reducer using the nitric oxide/nitrogen mixture;
• do not attempt to repair a defective valve;
• do not tighten the pressure reducer/flowmeter with pliers, as this may break the gasket and thus damage the delivery device;
• exhaust exhaled gases to the outside (avoiding areas where gas could accumulate). Before use, ensure the room has an adequate ventilation system for gases in case of accidents or accidental leaks;
• since nitric oxide is colorless and odorless, it is recommended to use a detection system in all rooms where it is used or stored;
• the American (NIOSH) and European agencies responsible for occupational safety and health recommend the following exposure limits for medical personnel:
  • NO: 25 ppm for 8 hours (30 mg/m³)
  • NO₂: 2 ppm (4 mg/m³)
• To comply with the above recommendations, an analysis of nitric oxide and nitrogen dioxide concentrations in the atmosphere must be performed;
• Installation of a nitric oxide delivery piping system, including a cylinder supply station, fixed network, and terminal units, is prohibited.