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 225 ppm, 450 ppm, 1000 ppm mol/mol

Read this leaflet carefully before starting to use this medicine, as it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any doubts, consult your doctor.
• This medicine has been prescribed for you only, and you must not give it to other people even if they have the same symptoms as you, as it may harm them.
• If you experience any adverse effects, consult your doctor, even if they are not listed in this leaflet. See section 4.

1. What is Neophyr and what it is used for

2. What you need to know before starting to use Neophyr

3. How to use Neophyr

4. Possible adverse effects

5. Storage of Neophyr

6. Contents of the pack and additional information

Neophyr is a gas mixture for inhalation use.

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

What is it used for?

Neophyr must 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. When inhaled, the gas mixture may improve blood flow within the lungs, which may contribute to increasing the amount of oxygen that reaches the baby's blood.

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

No use Neophyr:

• If you are allergic to nitric oxide or any of the other components of this medication (listed in section 6).
• If you (as a patient) or your child (as a patient) have abnormal heart circulation.
• If you (as a patient) or your child (as a patient) have 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 for you or your child.

Inhaled nitric oxide may affect the blood's ability to transport oxygen. This function will be monitored by taking blood samples, and if necessary, the dose of inhaled nitric oxide will be reduced.

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

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

No documented effects of inhaled nitric oxide have been reported in newborns with a congenital malformation that involves the diaphragm not being fully present (also known as "congenital diaphragmatic hernia").

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

Children

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

Use of Neophyr with other medications

Your doctor will decide when to treat you or your child with Neophyr and other medications, and will closely monitor the treatment.

Inform your doctor if you (as a patient) or your child (as a patient) are taking, have taken recently, or may need to take any other medication.

Some medications may affect the blood's ability to transport oxygen. These medications include prilocaine (a local anesthetic used to relieve pain in minor 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 sufficient oxygen while you are using these medications.

Pregnancy, breastfeeding, and fertility

Neophyr should not be used during pregnancy unless it is clearly necessary, such as in situations where life-support equipment needs to be applied.

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

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

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

For your safety (or that of your child), 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) 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 of 20 ppm for children and 40 ppm for adults) parts per million of the gas that you or your child inhale. The lowest effective dose will be applied.

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 cardiac surgery, Neophyr is usually administered for 24-48 hours. However, Neophyr therapy 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 controlled by taking blood samples, and if necessary, the dose of Neophyr will be reduced and medications 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 interrupt the Neophyr treatment

Neophyr treatment 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 Neophyr treatment is stopped suddenly without first reducing the dose.

At the end of treatment, the doctor will gradually reduce the amount of Neophyr prescribed for you or your child, allowing the circulation in the lungs to adjust to the amount of oxygen/air without Neophyr. This may take one or two days before you or your child complete the Neophyr treatment.

Follow exactly the administration instructions for this medication indicated by your doctor. In case of doubt, ask your doctor, pharmacist, or nurse.

Like all medications, this medication may produce adverse effects, although not all people will experience them.

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

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

• Low platelet count, abnormally low potassium concentration in the blood (hypokalemia), low blood pressure, shortness of breath or pulmonary collapse, abnormally high amounts of bilirubin pigment in the blood.

The adverse effects that may be observed, but whose frequency is unknown (cannot be estimated from available data) are:

• Pulmonary hypertension rebound effect (increase in pulmonary arterial pressure) and low oxygen levels in the blood (hypoxemia) due to sudden treatment withdrawal; increased methemoglobin levels and, therefore, reduced oxygen transport capacity.
• Accidental exposure to nitrogen oxide in the environment, for example, due to equipment or balloon leakage, may cause headaches.

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

If any of the adverse effects become severe, or if you observe any adverse effect that does not appear in this prospectus, inform your doctor.

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

Reporting Adverse Effects

If you experience any type of adverse effect, consult your doctor, even if it is possible adverse effects that do not appear in this prospectus. You can also report them directly through the Spanish System for Pharmacovigilance of Medicines for Human Use:www.notificaRAM.es.

By reporting adverse effects, you can contribute to providing more information about the safety of this medication.

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

Neophyr therapy should only be used and handled by hospital personnel.

• Neophyr cartridges must be stored in a way that they are secured to prevent them from falling or causing potential damage.

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

All regulations related to the handling of cartridges under pressure must be respected.

The storage will be supervised by specialists in the hospital. Gas cartridges must be stored in well-ventilated rooms or ventilated warehouses where they are protected from rain and direct sunlight.

Cartridges must be stored at a temperature between -10 and +50 °C.

Protect cartridges from impacts, falls, oxidizing or flammable materials, humidity, and heat or ignition sources.

Storage in the pharmacy department

Gas cartridges must be kept in a designated area exclusively for the storage of medicinal gases that is well-ventilated, clean, and locked with a key. This area must have a separate installation for the storage of nitric oxide gas cartridges.

Storage in the medical department

The gas cartridge must be placed in an area where there are suitable equipment to ensure that the cartridge remains in a vertical position.

When the cartridge is empty, it must not be disposed of with other waste: the supplier will collect the empty cartridges.

Do not use this medication after the expiration date that appears on the cartridge label. The expiration date is the last day of the month indicated.

Composition of Neophyr

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

Appearance of the product and contents of the packaging

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

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

or

Gas capsules 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 capsule filled to 150 bar contains approximately 1.77 kg of gas.

The capsules made from an aluminum alloy have a white body and a turquoise nose.

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

Holder of the marketing authorization and responsible for manufacturing

Holder of the marketing authorization

SOL FRANCE SUCURSAL EN ESPAÑA

Calle Yeso, num. 2

28500 Arganda del Rey - (Madrid)Spain

Responsible for manufacturing

SOL S.p.A.

Via Libertà 247

20900 Monza

Italy

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

Last review date of this leaflet: July 2018

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