NEOPHYR 450 PPM MOL/MOL COMPRESSED MEDICAL GAS

Introduction

Package Leaflet: Information for the User

Neophyr 225 ppm mol/mol, medicinal compressed gas

Neophyr 450 ppm mol/mol, medicinal compressed gas

Neophyr 1000 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.
• 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 get any side effects, talk to your doctor. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

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

1. What is Neophyr and what is it used for

Neophyr is a gas mixture for inhalation use.

Neophyr is a medicinal compressed gas consisting of a gas mixture containing 225 ppm, 450 ppm or 1000 ppm mol/mol of nitric oxide.

What is it used for?

Neophyr should be administered exclusively by healthcare professionals and is intended for strictly hospital use.

Neophyr is indicated in the following cases:

• Newborn babies with pulmonary insufficiency associated with high blood pressure in the lungs, a health problem known as hypoxic respiratory failure. By inhaling it, the gas mixture can improve blood flow within the lungs, which can contribute to increasing the amount of oxygen that reaches the baby's blood.

• Newborn babies, infants, children, and adolescents from 0-17 years and adults with high blood pressure in the lungs related to heart surgery. This gas mixture can improve heart function and increase blood flow within the lungs.

2. What you need to know before you use Neophyr

Do not use Neophyr:

• If you are allergic to nitric oxide or any of the other components of this medicine (listed in section 6).
• If you have been told that you (as a patient) or your child (as a patient) have abnormal circulation in the heart.
• If you (as a patient) or your child (as a patient) have a congenital or acquired deficiency of methemoglobin reductase (MetHb reductase) or glucose-6-phosphate dehydrogenase (G6PD).

Warnings and precautions

Consult your doctor before starting to use Neophyr.

Inhaled nitric oxide may not be effective in all cases, so other therapies may be considered necessary for you or your child.

Inhaled nitric oxide can affect the blood's ability to transport oxygen. This function will be monitored through blood sampling, and if necessary, the dose of inhaled nitric oxide will be reduced.

Nitric oxide can react with oxygen to form nitrogen dioxide, which can cause irritation of the respiratory tract. The doctor treating you or your child will monitor the nitrogen dioxide levels and, if high values are detected, will adjust the Neophyr therapy or reduce it as necessary.

Inhaled nitric oxide can mildly affect the platelets (components that contribute to blood clotting) in your body or your child's body, so the appearance of any signs of bleeding and/or bruising should be supervised. If you notice any signs or symptoms that may be associated with bleeding, you should inform your doctor directly.

No effects of inhaled nitric oxide have been documented in newborn babies with a malformation that means the diaphragm is not fully present (also called "congenital diaphragmatic hernia").

In newborn babies with special heart malformations, which doctors call "congenital heart disease", inhaled nitric oxide can cause a worsening of circulation.

Cases of fluid retention in the lungs have been reported with the use of nitric oxide in patients with disease due to a blocked or narrow vein in the lungs. If you (as a patient) or your child (as a patient) develop shortness of breath or difficulty breathing, contact your doctor immediately.

Children

Neophyr should not be used in premature babies with a gestational age of less than 34 weeks.

Using Neophyr with other medicines

Your doctor will decide when to treat you or your child with Neophyr and other medicines, as well as carefully monitor the treatment.

Tell your doctor if you (as a patient) or your child (as a patient) are taking, have recently taken, or might take any other medicines.

Some medicines can affect the blood's ability to transport oxygen. These medicines include prilocaine (a local anesthetic used to relieve pain in minor painful procedures, such as suturing and minor surgical or diagnostic procedures) or glyceryl trinitrate (used to treat chest pain). Your doctor will check that the blood can transport enough oxygen while you are using these medicines.

Pregnancy, breastfeeding, and fertility

Neophyr should not be used during pregnancy unless clearly necessary, as in situations where life-support equipment is required.

Exposure to nitric oxide should be avoided in humans during breastfeeding.

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor for advice before taking this medicine.

3. How to use Neophyr

Your doctor will decide on the correct dose of Neophyr and will administer Neophyr to you or your child in the lungs using a system designed for the administration of this gas. This system will ensure the administration of the correct amount of nitric oxide by diluting Neophyr with an oxygen/air mixture immediately before administering it to the patient.

For your safety (or your child's safety), the systems designed for the administration of Neophyr are equipped with devices that constantly measure the amount of nitric oxide, oxygen, and nitrogen dioxide (a chemical substance that forms when nitric oxide is mixed with oxygen) that is administered to the lungs.

Your doctor will decide how long the treatment with Neophyr should last for you or your child.

The recommended dose of Neophyr is 10 to 20 ppm (with a maximum dose for children of 20 ppm and for adults of 40 ppm) parts per million of the gas that you or your child inhale. The lowest effective dose will be used.

It is usually necessary to apply the therapy for about 4 days in newborn babies with pulmonary insufficiency associated with high blood pressure in the lungs. In children and adults with high blood pressure in the lungs associated with heart surgery, Neophyr is usually administered for 24-48 hours. However, the therapy with Neophyr may last longer.

If you use more Neophyr than you should

Excessive inhalation of nitric oxide can affect the blood's ability to transport oxygen. This function will be monitored through blood sampling, and if necessary, the dose of Neophyr will be reduced, and the administration of medicines such as vitamin C, methylene blue, or, if necessary, a blood transfusion, will be considered to improve the blood's oxygen transport capacity.

If you stop treatment with Neophyr

Treatment with Neophyr should not be stopped suddenly. It has been observed that low blood pressure or a rebound effect of increased pressure in the lungs occurs if the treatment with Neophyr is stopped suddenly without first reducing the dose.

At the end of the treatment, the doctor will gradually reduce the amount of Neophyr prescribed for you or your child, so that the circulation in the lungs can adjust to the amount of oxygen/air without Neophyr. Consequently, this may take one or two days before you or your child finish the treatment with Neophyr.

Follow the instructions for administration of this medicine exactly as your doctor has told you. If you are unsure, ask your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Your doctor will closely monitor and supervise any type of side effect. It is unlikely that you will suffer from these side effects.

The side effects that occur very frequently (affect more than 1 in 10 patients) associated with Neophyr therapy include:

• Low platelet count, abnormally low potassium levels in the blood (hypokalemia), low blood pressure, shortness of breath or lung collapse, abnormally high levels of bilirubin in the blood.

The side effects that may occur, but whose frequency is not known (cannot be estimated from the available data) are:

• Rebound effect of high blood pressure in the lungs (increase in pulmonary arterial pressure) and low oxygen levels in the blood (desaturation of oxygen/hypoxemia) due to sudden withdrawal of treatment; increased methemoglobin and, therefore, reduced oxygen transport capacity.
• Accidental exposure of nitric oxide to the ambient air, e.g., due to equipment leakage or cylinder leakage, can cause headache.

You should inform the staff directly if you experience a headache while you are near your child when Neophyr is being administered.

If any of the side effects become serious, or if you notice any side effects not listed in this leaflet, please tell your doctor.

If you have any further questions on the use of this product, ask your doctor or other healthcare professionals.

Reporting of side effects

If you get any side effects, talk to your doctor. This includes any possible side effects not listed in this leaflet. You can also report side effects directly through the Spanish Medicines and Healthcare Products Agency (AEMPS) website: http://www.aemps.gob.es/.

By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Neophyr

Keep this medicine out of the sight and reach of children.

Therapy with Neophyr should only be used and handled by hospital personnel.

• The Neophyr cylinders should be stored in such a way that they are secured so that they cannot fall or cause potential damage.

• Neophyr should be used and administered exclusively by personnel specially trained in the use and handling of this product.

All regulations regarding the handling of pressure cylinders must be respected.

Storage will be supervised by specialists in the hospital. The gas cylinders should be stored in well-ventilated rooms or ventilated warehouses where they are protected from rain and direct sunlight.

The cylinders should be stored at a temperature between -10 and +50 °C.

Protect the cylinders from shocks, falls, oxidizing or flammable materials, moisture, and heat or ignition sources.

Storage in the pharmacy department

The gas cylinders should be kept in a designated area exclusively for the storage of medicinal gases that is well-ventilated, clean, and locked. This area should have a special separate installation for the storage of nitric oxide gas cylinders.

Storage in the medical department

The gas cylinder should be placed in an area where there is equipment to ensure that the cylinder remains in a vertical position.

When the cylinder is empty, it should not be disposed of with other waste: the supplier will collect the empty cylinders.

Do not use this medicine after the expiry date which is stated on the label of the gas cylinder, after EXP. The expiry date is the last day of the month shown.

6. Contents of the pack and other information

Composition of Neophyr

• The active substance is nitric oxide 225 ppm mol/mol, 450 ppm mol/mol, or 1000 ppm mol/mol.
• The other component is nitrogen.

Appearance and packaging of the product

Gas cylinders with a capacity of 2 l (Neophyr 1000 ppm mol/mol).

A 2-liter gas cylinder filled to 150 bar contains approximately 0.35 kg of gas.

or

Gas cylinders with a capacity of 10 l (Neophyr 225 ppm mol/mol, Neophyr 450 ppm mol/mol, Neophyr 1000 ppm mol/mol).

A 10-liter gas cylinder filled to 150 bar contains approximately 1.77 kg of gas.

The cylinders made of an aluminum alloy have a white-painted body and a turquoise-painted tip.

They are equipped with a stainless steel residual pressure valve with a specific ISO 5145 (2004) type outlet connector.

Marketing authorization holder and manufacturer

Marketing authorization holder

SOL FRANCE SUCURSAL EN ESPAÑA

Calle Yeso, num. 2

28500 Arganda del Rey - (Madrid) Spain

Manufacturer

SOL S.p.A.

Via Libertà 247

20900 Monza

Italy

This medicine is authorized in the Member States of the European Economic Area under the following names:

Germany: Neophyr

Austria: Neophyr

Belgium: Neophyr

Bulgaria: Neophyr

Cyprus: Neophyr

Croatia: Neophyr

Slovenia: Neophyr

Spain: Neophyr

Greece: Neophyr

Ireland: Neophyr

Italy: Neophyr

Luxembourg: Neophyr

Netherlands: Neophyr

Romania: Neophyr

United Kingdom: Neophyr

Czech Republic: Iasophyr

Hungary: Noxphyr

Slovakia: Neophyr

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 Healthcare Products (AEMPS): http://www.aemps.gob.es/.

The following information is intended for healthcare professionals only.

[The full summary of product characteristics will be included below].