Inoxgen 400 ppm mol/mol medicinal compressed gas

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Inoxgen 400 ppm mol/mol medicinal compressed gas

Inoxgen 800 ppm mol/mol medicinal compressed gas

Inoxgen 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, as you may need to read it again.
• If you have any questions, consult your child's doctor or nurse.
• This medicine has been prescribed for you only, and you should not give it to other people, even if they have the same symptoms as you, because it may harm them.
• If you experience any adverse effects, consult your doctor, pharmacist, or nurse, even if they are adverse effects not listed in this leaflet. See section 4.

Contents of the leaflet:

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

1. What Inoxgen is and what it is used for

Inoxgen contains nitric oxide, a gas indicated for the treatment of:

• Newborns with 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, which may help increase the amount of oxygen delivered to the child's blood.
• Newborns, infants, children, adolescents aged 0–17 years, and adults with pulmonary hypertension related to heart surgery. This gas mixture may improve cardiac function and increase blood flow in the lungs, thereby helping to increase the amount of oxygen delivered to the blood.

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

Do not use Inoxgen:

• if you (as a patient) or your child (as a patient) are allergic (hypersensitive) to nitric oxide or to any of the other components of Inoxgen (listed in section 6)
• if you have been informed that you (as a patient) or your child (as a patient) have abnormal blood circulation in the heart.

Warnings and precautions

Consult your doctor or nurse before starting to use Inoxgen.

Inhaled nitric oxide may not always be effective; therefore, alternative therapies may need to be considered for you or your child.

Inhaled nitric oxide may affect the blood's ability to carry oxygen. This must be monitored through blood samples, and if necessary, the dose of inhaled nitric oxide should be reduced.

Nitric oxide may react with oxygen to form nitrogen dioxide, which can irritate the respiratory tract. You or your child's doctor may monitor nitrogen dioxide levels, and if elevated levels are detected, treatment with Inoxgen should be adjusted accordingly by reducing the dose.

Inhaled nitric oxide may have a slight effect on platelets (components that help blood clot) in you or your child, so signs of bleeding or bruising should be observed. If you notice any signs or symptoms that may indicate bleeding, inform the doctor immediately.

Cases of fluid retention in the lungs have been reported with nitric oxide in patients who have a disease caused by a blocked or narrowed vein in the lungs. If you (as a patient) or your child (as a patient) experience shortness of breath or difficulty breathing, contact your doctor immediately.

No effects have been documented in newborn infants with malformations where the diaphragm is not fully formed, also known as "congenital diaphragmatic hernia".

In newborn infants with certain specific heart malformations, what doctors call "congenital heart disease", the use of inhaled nitric oxide may worsen circulation.

Children

The use of Inoxgen is not recommended in premature infants < 34 weeks of gestation.

Other medicines and Inoxgen

The doctor will decide when to treat you or your child with Inoxgen and other medications, and will carefully monitor the treatment.

Inform your doctor if you (as a patient) or your child (as a patient) are using, or have recently used, any other medicines.

Some medicines may affect the blood's ability to carry oxygen. These include prilocaine (a local anesthetic used to relieve pain during minor painful procedures such as suturing or minor surgical or diagnostic procedures) or glyceryl trinitrate (used to treat angina pectoris). Your doctor will check that the blood contains sufficient oxygen when these medicines are being used.

Pregnancy and breastfeeding

The use of Inoxgen should be avoided during pregnancy and breastfeeding.

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

Consult your doctor or pharmacist before starting to take any medicine.

3. How to use Inoxgen

Follow exactly the administration instructions for this medicine as given by your doctor. If in doubt, consult your doctor again.

Your doctor will determine the correct dose of Inoxgen and will administer Inoxgen to your lungs or to those of your child using a system designed for delivery of this gas. This delivery system will ensure that the correct amount of nitric oxide is administered by diluting Inoxgen with an oxygen/air mixture immediately before administration.

For your safety or that of your child, the systems intended for Inoxgen administration are equipped with devices that continuously measure the amounts of nitric oxide, oxygen, and nitrogen dioxide (a chemical formed when nitric oxide is mixed with oxygen) being delivered to the lungs.

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

The recommended dose of Inoxgen is 10 to 20 ppm (maximum dose of 20 ppm for children and 40 ppm for adults) parts per million of inhaled gas for you or your child. The lowest effective dose should be sought.

Treatment typically lasts about 4 days in newborns with pulmonary insufficiency associated with high blood pressure in the lungs. In children and adults with pulmonary hypertension associated with heart surgery, Inoxgen is usually administered for 24–48 hours. However, treatment with Inoxgen may be prolonged.

If you use more Inoxgen than you should

Excessive inhaled nitric oxide may affect the blood's ability to carry oxygen. This will be monitored through blood samples, and if necessary, the amount of Inoxgen will be reduced. Medications such as vitamin C, methylene blue, or possibly a blood transfusion may also be considered to improve oxygen-carrying capacity.

If you stop treatment with Inoxgen

Treatment with Inoxgen must not be stopped abruptly.

Cases of low blood pressure or a rebound effect with increased pressure in the lungs have occurred when Inoxgen treatment was suddenly discontinued without prior dose reduction.

Your doctor will gradually reduce the prescribed amount of Inoxgen for you or your child as treatment nears completion, allowing the lung circulation to adjust to oxygen/air without Inoxgen. Consequently, it may take one or two days before you or your child completely stop Inoxgen treatment.

If you have any further questions about the use of this medicine, ask your doctor.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone experiences them.

Your doctor will monitor you or your child for adverse effects.

Very common adverse effects (may affect more than 1 in 10 patients) associated with Inoxgen treatment include:

• Low platelet count

Frequent adverse effects (may affect up to 1 in 100 people) associated with Inoxgen treatment include:

• Hypotension, shortness of breath, or lung collapse.

Adverse effects that may occur and are uncommon (affect between 1 in 100 and 1 in 1,000 patients) are:

• Increase in methemoglobin, and therefore reduced oxygen-carrying capacity.

Adverse effects observed with unknown frequency (cannot be estimated from available data) are:

• Bradycardia (low heart rate) or excessively low blood oxygen levels (oxygen desaturation/hypoxemia) due to sudden interruption of treatment.

• Headache, dizziness, dry throat, or breathing difficulty following accidental exposure to nitric oxide in ambient air (e.g., equipment or cylinder leak).

You should inform the medical staff directly if you experience headache while being near your child during Inoxgen administration.

Reporting of adverse effects

If you experience any type of adverse effect, consult your doctor, pharmacist, or nurse, even if it is a possible adverse effect not listed in this leaflet. You may also report them directly via the Spanish Pharmacovigilance System for Human Medicines: www.notificaRAM.es

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

5. Storage of Inoxgen

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

Do not use this medicine after the expiry date stated on the container. The expiry date refers to the last day of the month indicated.

All regulations concerning the handling of pressurized containers must be followed.

Gas cartridges must be protected to prevent breakage or falls.

They must be kept away from any oxidizing or flammable materials, moisture, heat sources, or sources of ignition, and stored at a temperature between -10°C and +50°C.

Cartridges must be protected against breakage, falls, oxidizing and flammable materials, moisture, heat sources, or sources of ignition.

Storage in the pharmacy department

Cartridges must be stored in a ventilated, clean, and locked area, designated exclusively for the storage of medical gas. Within this area, a separate installation must be provided specifically for the storage of nitric oxide cartridges.

Storage in the medical department

The cartridge must be placed in a location equipped with appropriate equipment to ensure it remains in an upright position.

Cartridges must be stored in well-ventilated areas.

When the cartridge is empty, do not dispose of it. The supplier will collect empty gas cartridges.

6. Contents of the pack and other information

Composition of Inoxgen

The active substance is nitric oxide 400 ppm mol/mol, 800 ppm mol/mol and 1000 ppm mol/mol.

The other component is: nitrogen.

Appearance of the product and pack contents

Inoxgen is an inhalation gas supplied in aluminum cylinders at a pressure of 150 bar at 15°C, equipped with a positive pressure valve made of stainless steel or brass.

The gas cylinders are available in the following water volumes expressed in liters: 5 L, 10 L, 20 L, 40 L, and 50 L.

• 5 L cylinder containing 0.75 m³ of gas weighing 0.85 kg.
• 10 L cylinder containing 1.5 m³ of gas weighing 1.7 kg.
• 20 L cylinder containing 3.0 m³ of gas weighing 3.4 kg.
• 40 L cylinder containing 6.0 m³ of gas weighing 6.8 kg.
• 50 L cylinder containing 7.5 m³ of gas weighing 8.5 kg.

Only certain pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

NIPPON GASES ESPAÑA, S.L.U.
C/ Orense, 11
28020 Madrid, Spain

Manufacturer

Nippon Gases España S.L.U.
Calle Embajadores 474
28053 Madrid, Spain

Nippon Gases Pharma S.R.L.
Via Martino Della Torre 16
28100 Novara (NO), Italy

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

Date of the most recent review of this leaflet: January 2026

Other sources of information

Detailed and up-to-date information on this medicinal product is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es/

This information is intended solely for healthcare professionals:

Dosage

Persistent pulmonary hypertension in the newborn (PPHN)

Inoxgen shall only be used once respiratory support has been optimized. The recommended maximum dose of Inoxgen is 20 ppm. It is recommended not to exceed the maximum dose of 20 ppm. The maximum dose may exceptionally be increased according to the patient's response.

Inoxgen is used in ventilated neonates in whom assisted ventilation is expected to last > 24 hours. As soon as possible, and within the first 4–24 hours of therapy, the dose should be reduced to 5 ppm, provided arterial oxygenation remains adequate at this lower dose.

Inhaled nitric oxide therapy should be maintained at 5 ppm until improvement in neonatal oxygenation is observed such that the FiO2 (fraction of inspired oxygen) is < 0.60.

Treatment may be continued for up to 96 hours or until resolution of oxygen desaturation and until the neonate is ready for gradual withdrawal of Inoxgen therapy. The duration of treatment is variable, typically less than 4 days.

Gradual withdrawal

Withdrawal of Inoxgen therapy should be attempted once assisted ventilation has substantially decreased or after 96 hours of treatment. When the decision to discontinue inhaled nitric oxide therapy is made, the dose should be reduced by 1 ppm every 30 or 60 minutes according to the prescription. If there are no changes in oxygenation during administration of Inoxgen at 1 ppm (the FiO2 should be increased by 10%), administration of Inoxgen should be discontinued and the neonate should be closely monitored for signs of hypoxemia. If oxygenation drops by more than 20%, Inoxgen therapy should be resumed at 5 ppm and discontinuation should be reconsidered after 12 to 24 hours.

Pulmonary hypertension associated with cardiac surgery

Inoxgen shall only be used after conservative treatment has been optimized.

Newborns, infants, children, and adolescents aged 0 to 17 years: The initial dose of inhaled nitric oxide is 10 ppm (parts per million) of inhaled gas. The dose may be increased up to 20 ppm if the minimal dose has not produced sufficient clinical effects. The lowest effective dose should be administered and then gradually reduced to 5 ppm, provided pulmonary arterial pressure and systemic arterial oxygenation remain adequate at this lower dose.

Adults: The initial dose of inhaled nitric oxide is 20 ppm (parts per million) of inhaled gas. This dose may be increased up to 40 ppm if the minimal dose has not produced sufficient clinical effects. The lowest effective dose should be administered and then gradually reduced to 5 ppm, provided pulmonary arterial pressure and systemic arterial oxygenation remain adequate at this lower dose. Discontinuation of treatment should be considered if no beneficial physiological effects are observed after a 30-minute test period.

In children and adults with pulmonary hypertension associated with cardiac surgery, Inoxgen is typically administered for 24–48 hours. However, Inoxgen treatment may be prolonged.

Gradual withdrawal

Gradual withdrawal of Inoxgen therapy should be attempted once hemodynamic parameters have stabilized, along with weaning from ventilation and inotropic support.

The dose should be progressively reduced to 1 ppm over 30 minutes, with continuous monitoring of systemic and central pressures, followed by disconnection. Gradual withdrawal should be attempted at least every 12 hours when the patient is stable on a low dose of Inoxgen.

Instructions for use/administration

All equipment, including connectors, tubes, and circuits, used in the administration of nitric oxide must be made of materials compatible with the gas.

From the standpoint of corrosion, the delivery system can be divided into two zones: 1) from the gas cylinder valve to the humidifier (dry gas), and 2) from the humidifier to the outlet (moist gas which may contain NO2).

Studies show that dry nitric oxide mixtures can be used with most materials. However, the presence of nitrogen dioxide and moisture creates an aggressive environment.

Among metallic construction materials, only stainless steel is recommended. The polymeric materials analyzed that may be used in nitric oxide delivery systems include polyethylene (PE) and polypropylene (PP).

Butyl rubber, polyamide, and polyurethane should not be used. Polychlorotrifluoroethylene, hexafluoropropylene-vinylidene copolymer, and polytetrafluoroethylene have been extensively used with pure nitric oxide and other corrosive gases. They are considered inert, and therefore do not require testing.

To prevent any incidents, the following instructions must be strictly observed:

• Before use, the condition of the equipment must be checked.
• Gas cylinders must be secured and kept upright to prevent accidental falls.
• The valve must not be opened abruptly.
• Do not use the cylinder if the valve is not protected by a cap or cover.
• A specific medical-grade connection must be used, fully compliant with guidelines, along with a pressure regulator capable of withstanding a pressure of at least 1.5 times the maximum possible operating pressure (200 bar) of the cylinder.
• The pressure regulator must be purged with the nitrogen/nitric oxide mixture before each new use to prevent inhalation of nitrogen dioxide.
• If the valve is defective, do not attempt to repair it.
• The pressure regulator must not be tightened with pliers, as this could damage the gasket.