Prospect: 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 this prospect carefully before starting to use this medication, as it contains important information for you.

• Keep this prospect, as you may need to read it again.
• If you have any doubts, consult your doctor or nurse.
• This medication has been prescribedonlyto you, 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 adverse effects, consult your doctor, pharmacist, or nurse, even if they are not listed in this prospect. See section 4

1. What is Inoxgen and how it is used.

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

3. How to use Inoxgen

4. Possible adverse effects.

5. Storage of Inoxgen

6. Contents of the package and additional information.

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

• Newborns with pulmonary insufficiency associated with elevated pulmonary arterial pressure, a condition known as hypoxic respiratory failure. When inhaled, this gaseous mixture may improve blood flow through the lungs, which may contribute to increasing the amount of oxygen that reaches the baby's blood.
• Newborns, infants, children, and adolescents aged 0-17 years and adults with pulmonary hypertension related to cardiac surgery. This gaseous mixture may improve cardiac function and increase blood flow in the lungs, which may help to increase the amount of oxygen that reaches the blood.

No use Inoxgen:

- If you (as a patient) or your child (as a patient) are allergic (hypersensitive) to nitric oxide or 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 heart circulation.

Warnings and precautions

Consult your doctor or nurse before starting to use Inoxgen

The inhaled nitric oxide may not always be effective, therefore, it may be necessary to consider alternative therapies for you or your child.

The inhaled nitric oxide may affect the blood's oxygen-carrying capacity. This must be monitored through blood samples and, if necessary, the dose of inhaled nitric oxide must be reduced.

The nitric oxide may react with oxygen to form nitrogen dioxide, which may irritate the respiratory tract. You or your child's doctor may monitor the nitrogen dioxide levels and, in the case of high levels, adjust the Inoxgen treatment, reducing it accordingly.

The inhaled nitric oxide may have a mild influence on platelets (components that help blood coagulation) or your child's, so it must be observed and any sign of bleeding or hematoma. If you observe any sign or symptom that could be associated with bleeding, you must inform your doctor directly.

No adverse effects have been documented in newborns with congenital diaphragmatic hernia, also known as "congenital diaphragmatic hernia".

In the case of newborns with special heart malformations, which doctors call "congenital heart disease", the use of inhaled nitric oxide may worsen circulation.

Children

Do not recommend the use of Inoxgen in premature children

Other medications and Inoxgen

Your doctor will decide when to treat you or your child with Inoxgen and other medications, and will closely 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 medication.

Some medications may affect the blood's ability to transport oxygen. These include prilocaine (a local anesthetic used to relieve pain in minor procedures, such as sutures or minor surgical or diagnostic procedures) or glyceryl trinitrate (used to treat angina). Your doctor will check that the blood contains sufficient oxygen when taking these medications.

Pregnancy and breastfeeding

Use of Inoxgen should be avoided during pregnancy and breastfeeding.

If you are pregnant or breastfeeding, believe you may be pregnant, or intend to become pregnant, consult your doctor before using Inoxgen

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

Follow exactly the administration instructions of this medication as indicated by your doctor.In case of doubt, consult your doctor again.

Your doctor will determine the correct dose of Inoxgen and administer Inoxgen to your lungs or your child's lungs through a system designed for the administration of this gas. This administration 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 your child's safety, the systems designed for Inoxgen administration are equipped with devices that constantly measure the amount of nitric oxide, oxygen, and nitrogen dioxide (a chemical substance obtained by mixing nitric oxide and oxygen) being administered to the lungs.

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

The recommended dose of Inoxgen is 10 to 20 ppm (maximum dose for children is 20 ppm and for adults is 40 ppm) parts per million of gas for inhalation by you or your child. Seek the most effective dose at the lowest level.

Typically, treatment is required for around 4 days in newborns with pulmonary insufficiency associated with high blood pressure in the lungs.In children and adults with pulmonary hypertension associated with cardiac surgery, Inoxgen is normally administered for 24-48 hours. However, Inoxgen treatment may be prolonged.

If you use more Inoxgen than you should

Excessive inhalation of nitric oxide may affect the blood's ability to transport oxygen. This will be controlled through blood samples, and if necessary, the amount of Inoxgen will be reduced, as well as the administration of medications such as vitamin C, methylene blue, or eventually a blood transfusion to improve oxygen transport capacity.

If you interrupt the treatment with Inoxgen

The Inoxgen treatment should not be stopped abruptly.

There have been cases of low blood pressure or a rebound effect of increased pressure in the lungs when Inoxgen treatment is suddenly suspended without first reducing the dose.

Your doctor will gradually reduce the amount of Inoxgen prescribed for you or your child when the treatment is about to end, to allow the lung circulation to adjust to oxygen/air without Inoxgen. Consequently, this may take one or two days before you or your child complete the Inoxgen treatment.

If you have any other doubts about the use of this medication, ask your doctor.

Like all medications,this medicationmay cause adverse effects, although not all people will experience them.

Your doctor will examine you or your child about adverse effects.

Very frequent 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 100people)associated with Inoxgen treatment include:

-Hypotension, shortness of breath, or pulmonary collapse.

Adverse effects that may be observed, which are infrequent(affect between 1 patient in 100 and 1 patient in 1000)are:

-Increased methemoglobin, and therefore reduced oxygen transport capacity.

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

-Bradycardia (low heart rate) or excessively low oxygen levels in the blood (hypoxemia) due to sudden interruption of treatment.

-Headache, dizziness, dry throat, or respiratory difficulty after accidental exposure to ambient air nitric oxide (e.g., equipment or balloon escape).

You should inform staff directly if you experience headache while near your child when receiving Inoxgen.

Reporting 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 prospectus. You can also report them directly to the Spanish System for Pharmacovigilance of Medicinal Products 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.

Do not usethis medicationafter the expiration date that appears on the packaging. The expiration date is the last day of the month indicated.

All guidelines related to the handling of pressure containers must be followed.

Oxygen cartridges must be protected to prevent breakage or falls.

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

Oxygen cartridges must be protected to prevent breakage, falls, combustible or flammable materials, moisture, heat sources or ignition sources.

Storage in the pharmacy department

Oxygen cartridges must be stored in a well-ventilated, clean, and locked area, exclusively for the storage of medicinal gas. Within that area, there must be a separate installation dedicated to the storage of nitric oxide cartridges.

Storage in the medical department

The cartridge must be placed in an area equipped with suitable material to maintain it upright.

Oxygen cartridges must be stored in well-ventilated areas.

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

Composition of Inoxgen

The active principle 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 contents of the container

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

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

5L cylinder with 0.75 m3 of gas weighing 0.85 kg.

10L cylinder with 1.5 m3 of gas weighing 1.7 kg 20L cylinder with 3.0 m3 of gas weighing 3.4 kg

40L cylinder with 6.0 m3 of gas weighing 6.8 kg 50L cylinder with 7.5 m3 of gas weighing 8.5 kg

Only some sizes of packaging may be commercially available.

Holder of the marketing authorization and responsible for manufacturing

Holder of the marketing authorization

NIPPON GASES ESPAÑA, S.L.U.

c/ Orense, 11

28020 Madrid

Responsible for manufacturing

Nippon Gases España S.L.U.

Calle Embajadores 474,.

28053 Madrid.

Spain

This medicinal product is authorized in the member states of the European Economic Area with the following names

Last review date of this leaflet:February 2021

Other sources of information

Detailed and updated information on this medicinal product is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS)http://www.aemps.gob.es/

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This information is intended solely for healthcare professionals:

Dosage

Persistent pulmonary hypertension in the newborn (HPPN)

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

Inoxgen is used in ventilated newborns whose assisted ventilation is expected to be > 24 hours. As soon as possible, and in the first 4-24 hours of therapy, the dose should be reduced to 5 ppm whenever the arterial oxygenation is adequate at this lower dose.

Inhaled nitric oxide therapy should be maintained at 5 ppm until improvement in the neonate's oxygenation is observed, so that FiO2 is <0.60.

Treatment can be continued until 96 hours or until the oxygen desaturation has been resolved and the neonate is ready for the gradual withdrawal of treatment with Inoxgen. Treatment duration is variable, usually less than 4 days.

Gradual withdrawal

Attempt to withdraw treatment with Inoxgen once assisted ventilation has decreased substantially or after 96 hours of treatment. When the decision is made to interrupt nitric oxide inhalation therapy, the dose should be reduced at a rate of 1 ppm every 30 or 60 minutes as prescribed. If there are no changes in oxygenation during administration of Inoxgen at 1 ppm (FiO2 should be increased by 10%), treatment with Inoxgen should be interrupted and the neonate should be closely monitored for signs of hypoxemia. If oxygenation falls by more than 20%, treatment with Inoxgen should be resumed at 5 ppm and the interruption should be re-evaluated after 12-24 hours.

Pulmonary hypertension associated with cardiac surgery

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

Newborns, infants, children, and adolescents from 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 to 20 ppm if the minimum dose has not produced sufficient clinical effects. The effective minimum dose should be administered, followed by a gradual reduction to 5 ppm whenever the pulmonary arterial pressure and systemic arterial oxygenation are 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 to 40 ppm if the minimum dose has not produced sufficient clinical effects. The effective minimum dose should be administered, followed by a gradual reduction to 5 ppm whenever the pulmonary arterial pressure and systemic arterial oxygenation are adequate at this lower dose. Discontinuation of treatment should be considered if no beneficial physiological effects are observed after a 30-minute test treatment.

Inoxgen is usually administered for 24-48 hours in children and adults with pulmonary hypertension associated with cardiac surgery. However, treatment with Inoxgen may be prolonged.

Gradual withdrawal

Attempt to withdraw treatment with Inoxgen once hemodynamic parameters have stabilized, along with the withdrawal of ventilation and inotropic support.

The dose should be gradually reduced to 1 ppm over 30 minutes while continuously monitoring systemic and central pressures. 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 point of view of corrosion, the administration system can be divided into two zones: 1) from the cylinder valve to the humidifier (dry gas) and 2) from the humidifier to the outlet (wet gas that may contain NO2).

Studies have shown that dry nitric oxide mixtures can be used with most materials. However, the presence of nitrogen dioxide and humidity creates an aggressive atmosphere.

Among metal construction materials, only stainless steel is recommended. The polymers analyzed that can be used in nitric oxide administration systems include polyethylene (PE) and polypropylene (PP).

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

To avoid any incidents, the following instructions must be strictly followed.

- Before use, the good condition of the material must be checked.

- Cylinders must be removed and securely fastened to prevent accidental falls.

- The valve should not be opened violently.

- If the cylinder valve is not protected by a cap or cover, do not use the cylinder.

- A specific medical-use connector and a pressure regulator that can withstand a pressure at least 1.5 times the maximum operating pressure (200 bar) of the cylinder must be used.

- The pressure regulator must be purged with the nitric oxide/nitrogen 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 should not be tightened with pliers, as this may damage the seal.