Neophyr

PATIENT INFORMATION LEAFLET

Neophyr 225 ppm mol/mol medicinal gas, compressed, 450 ppm mol/mol medicinal gas, compressed, 1000 ppm mol/mol medicinal gas, compressed

Nitric oxide 225 ppm, 450 ppm, 1000 ppm mol/mol
Please read this leaflet carefully before using this medicine as it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, consult your doctor.
• This medicine has been prescribed for you only. Do not give it to others, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, consult your doctor. See section 4.

Contents of this leaflet:

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

1. WHAT NEOPHYR IS AND WHAT IT IS USED FOR

Neophyr is a gas mixture for inhalation use.
Neophyr is a medicinal compressed gas composed of a gas mixture 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 strictly intended for
hospital use only.
Neophyr is indicated under the following conditions:

• newborns suffering from respiratory failure associated with high blood pressure in the lungs, a condition known as hypoxic respiratory failure. When inhaled, this gas mixture can improve blood flow through the lungs, thereby increasing the amount of oxygen reaching the child's blood.
• newborns, infants, children, adolescents aged 0 to 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 through the lungs.

2. WHAT YOU SHOULD KNOW BEFORE USING NEOPHYR

Do not use Neophyr:

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

Warnings and precautions
Talk to your doctor before using Neophyr.
Inhaled nitric oxide may not always be effective, and therefore other treatments may be considered necessary for you or for the child.
Inhaled nitric oxide can alter the blood's ability to carry oxygen. This effect will be monitored through blood samples, and if necessary, the dose of inhaled nitric oxide should be reduced.
Nitric oxide can react with oxygen to form nitrogen dioxide, which may cause airway irritation. Your doctor or pediatrician will monitor nitrogen dioxide levels, and if elevated levels are detected, Neophyr therapy will be adjusted and reduced accordingly.
Inhaled nitric oxide may have a weak effect on platelets (components involved in blood clotting); therefore, any signs of bleeding or bruising in you or in the child should be closely monitored. If signs or symptoms suggestive of bleeding occur, inform your doctor immediately.
No effect of inhaled nitric oxide has been documented in newborns with malformations due to incomplete diaphragm, the so-called "congenital diaphragmatic hernia".
In newborns with specific heart malformations, known by doctors as "congenital heart defects", inhaled nitric oxide may worsen circulation.

Children
Neophyr must not be administered to premature infants with less than 34 weeks of gestation.

Other medicines and Neophyr
Your doctor will decide when to treat you or the child with Neophyr and other medicines, under careful supervision of the treatment.
Inform your doctor if you (as a patient) or the child (as a patient) are taking, have recently taken, or might take any other medicines.
Some medicines can affect the blood's ability to carry oxygen. These include prilocaine (a local anesthetic used to relieve pain from minor painful procedures, such as suturing, and minor diagnostic or surgical procedures) or glyceryl trinitrate (used to treat chest pain). Your doctor will check that sufficient oxygen-carrying capacity of the blood is maintained during treatment with these drugs.

Pregnancy, breastfeeding and fertility
Neophyr must not be used during pregnancy unless clearly necessary, such as in life-support situations.
Women who are breastfeeding should avoid exposure to nitric oxide.
If you are pregnant, suspect you may be pregnant, planning to become pregnant, or are breastfeeding, ask your doctor for advice before taking this medicine.

3. HOW TO USE NEOPHYR

The doctor will determine the correct dose of Neophyr and will administer Neophyr into your lungs or those of your child through a system specifically designed to deliver this gas. This system ensures the correct amount of nitric oxide is administered by diluting Neophyr with an oxygen/air mixture immediately before delivery.
For your safety or that of the child, the systems intended for the administration of Neophyr are equipped with devices that continuously monitor the levels of nitric oxide, oxygen, and nitrogen dioxide (a chemical formed when nitric oxide mixes with oxygen) delivered to the lungs.
The doctor will decide the duration of treatment with Neophyr.
Neophyr is administered at doses ranging from 10 to 20 ppm (maximum dose 20 ppm in children and 40 ppm in adults), that is, parts per million of gas inhaled by you or your child. The lowest effective dose will be identified.
Treatment is usually required for about 4 days in newborns with respiratory failure associated with high blood pressure in the lungs. In children and adults with elevated pulmonary blood pressure related to heart surgery, Neophyr is typically administered for 24–48 hours. However, Neophyr therapy may last longer.

If you receive more Neophyr than prescribed
Excessive inhalation of nitric oxide may affect the blood's ability to carry oxygen. This will be monitored through blood samples, and if necessary, the dose of Neophyr will be reduced. Administration of medications such as vitamin C or methylene blue may be considered, or possibly blood transfusion, to improve the blood's oxygen-carrying capacity.

If you stop Neophyr treatment
Treatment with Neophyr must not be stopped abruptly. It is known that sudden discontinuation of Neophyr without first reducing the dose may lead to a drop in blood pressure or a rebound increase in pulmonary pressure.
At the end of treatment, the doctor will gradually reduce the amount of Neophyr administered to you or your child so that circulation in the lungs can adjust to oxygen/air without Neophyr. Therefore, it may take one or two days before you or your child completely stop Neophyr therapy.

If you have any doubts about the use of this medicine, consult your doctor or another healthcare professional.

4. POSSIBLE ADVERSE REACTIONS

Like all medicines, this medicine can cause adverse reactions, although not everyone experiences them.
Your doctor will carefully monitor and evaluate any adverse reactions. It is unlikely that such adverse reactions will occur.

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

• low platelet count, abnormally low blood potassium levels (hypokalemia), low blood pressure, hypoxic or collapsed lung, abnormally high levels of bile pigment (bilirubin) in the blood.

Adverse reactions observed but with unknown frequency (frequency cannot be estimated from the available data) are:

• rebound increase in pulmonary blood pressure (increased pressure in the pulmonary artery) and abnormally low blood oxygen levels (oxygen desaturation/hypoxemia) due to sudden interruption of treatment, increased methemoglobin levels and consequently reduced oxygen-carrying capacity.
• Accidental environmental airborne exposure to nitric oxide, for example due to a leak from equipment or cylinder, may cause headache.

You must immediately inform healthcare personnel if you experience headache when near a child being treated with Neophyr.
If any of the adverse reactions worsen or if you notice any adverse reactions not listed in this leaflet, inform your doctor.
If you have any doubts about the use of this medicine, consult your doctor or another healthcare professional.

Reporting of adverse reactions
If you experience any adverse reaction, including those not listed in this leaflet, consult your doctor. You may also report adverse reactions directly via the national reporting system at: https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting adverse reactions, you can help provide more information on the safety of this medicine.

5. HOW TO STORE NEOPHYR

Keep this medicine out of the sight and reach of children.
Treatment with Neophyr must be carried out and managed only by hospital personnel.

• Neophyr cylinders must be securely stored to prevent falling and thus avoid potential injury risks.
• Neophyr must be used and administered exclusively by personnel specifically trained in the use and handling of Neophyr.

All relevant safety rules for handling pressurized cylinders must be observed.
Storage at the hospital is supervised by specialists. Cylinders must be
stored indoors in well-ventilated areas, or outdoors in ventilated sheds, protected from
rain and direct sunlight.
Cylinders must be stored at a temperature between -10°C and +50°C.
Protect cylinders from impact, falls, oxidizing and flammable materials, moisture, heat sources, or ignition sources.
Storage in the pharmacy department
Cylinders must be stored in a well-ventilated, clean, and locked area,
reserved exclusively for the storage of medicinal gases. Within this area, a separate section must be designated for the storage of nitrous oxide cylinders.
Storage in the medical department
The cylinder must be stored in a specially designed area to keep the cylinder in an upright position.
Do not dispose of empty cylinders. Empty cylinders will be collected by the supplier.
Do not use this medicine after the expiry date stated on the cylinder label. The expiry date refers to the last day of that month.

6. CONTENTS OF THE PACKAGE AND OTHER INFORMATION

What Neophyr contains

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

Description of the appearance of Neophyr and contents of the package
Cylinders with a capacity of 2 l (Neophyr 1000 ppm mol/mol).
A 2-litre cylinder filled to 150 bar contains approximately 0.35 kg of 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-litre cylinder filled to 150 bar contains approximately 1.77 kg of gas.
The aluminium alloy cylinders have a white body and turquoise shoulder.
They are equipped with a residual pressure valve made of stainless steel and a specific outlet connector ISO 5145 (2004).

Marketing Authorization Holder and Manufacturer
Marketing Authorization Holder
SOL S.p.A.
Via Borgazzi 27
20900 Monza
Italy

Manufacturer
SOL S.p.A.
Via Libertà 247
20900 Monza
Italy

This medicinal product is authorized in the European Economic Area countries under the following names:
Austria: Neophyr
Belgium: Neophyr
Bulgaria: Neophyr
Croatia: Neophyr
Cyprus: Neophyr
Germany: Neophyr
Greece: Neophyr
Ireland: Neophyr
Italy: Neophyr
Luxembourg: Neophyr
Netherlands: Neophyr
Romania: Neophyr
Slovenia: Neophyr
Spain: Neophyr
United Kingdom: Neophyr

The following information is intended for healthcare professionals only.
SUMMARY OF PRODUCT CHARACTERISTICS