NOXAP 800 PPM MOL/MOL COMPRESSED MEDICAL GAS

Introduction

Package Leaflet: Information for the User

NOXAP 800 ppm mol/mol, medicinal gas, compressed

Nitric oxide

Read this package leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this package leaflet, you may need to read it again. If you have any further questions, ask your doctor or pharmacist.
• If you experience side effects, ask your doctor or pharmacist, even if they are not listed in this package leaflet. See section 4.

Contents of the package leaflet

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

1. What is NOXAP and what is it used for

NOXAP is a mixture of gases for inhalation use.

NOXAP is a medicinal gas, compressed, consisting of a mixture of gases containing 200 ppm mol/mol of nitric oxide.

What are its uses?

NOXAP should only be administered by healthcare professionals and is for use strictly in hospitals. NOXAP is indicated in the following cases:

In newborns with lack of oxygen in the blood (hypoxemic respiratory failure) related to different causes.

NOXAP improves oxygenation and reduces the need for circulation

In pediatric and adult patients undergoing cardiac surgery with acute high blood pressure in the lungs(pulmonary hypertension). NOXAP reduces pulmonary hypertension and the risk of right heart failure.

2. What you need to know before you start using NOXAP

Do not take NOXAP in the following cases:

• Newborns with proven dependence on right-to-left shunt or those suffering from significant left-to-right shunt.
• Patients with congenital or acquired deficiency of methemoglobin reductase (MetHb reductase) or glucose-6-phosphate dehydrogenase (G6PD).

Be cautious when using NOXAP:

• In patients with left ventricular dysfunction, NOXAP may cause heart failure and pulmonary edema.
• In patients with complex congenital heart defects.

Use of other medicines

Tell your doctor if you are using or have recently used other medicines, including those obtained without a prescription.

Oxygen:In the presence of oxygen, nitric oxide is rapidly oxidized, producing substances that are toxic to the lungs. To avoid this situation, continuous monitoring should be performed during treatment with NOXAP.

NO donors:Cardiovascular medications such as sodium nitroprusside and nitroglycerin may have an additive effect to that of NOXAP, increasing the risk of methemoglobinemia.

Drugs that increase methemoglobin concentrations: When drugs such as alkyl nitrates, sulfonamides, and prilocaine are administered with nitric oxide, there is an increased risk of methemoglobinemia.

Synergistic effects have been reported with the administration of vasoconstrictors (almitrine, phenylephrine), prostacyclin, and phosphodiesterase inhibitors, without increasing adverse reactions.

Inhaled nitric oxide has been used at the same time as tolazoline, dopamine, dobutamine, norepinephrine, steroids, and surfactants, without any observed interactions.

Your doctor will decide if NOXAP can be used with other medicines and will closely monitor your treatment.

Pregnancy and breastfeeding

NOXAP should not be used during pregnancy unless the woman's clinical condition requires treatment with NOXAP.

Harmful effects may be expected since methemoglobin is considered harmful to the fetus and nitric oxide has demonstrated genotoxic potential through the induction of structural alterations in DNA.

Breastfeeding should be interrupted during treatment with NOXAP.

Driving and using machines

No studies have been reported on the ability to drive and use machines.

3. How to use NOXAP

NOXAP should only be administered by healthcare professionals and is for use strictly in hospitals.

NOXAP is administered by inhalation through a system that delivers the prescribed concentration of nitric oxide to the lungs, by diluting NOXAP in a mixture of oxygen and air.

Your doctor will determine the dosage and duration of your treatment with NOXAP.

If you take more NOXAP than you should,the administration system will activate a warning signal. Then, your doctor will decrease or stop the administration of NOXAP and subsequently determine the most appropriate treatment to follow.

If you stop treatment with NOXAP

Your doctor will gradually decrease the dosage of NOXAP until the end of treatment.

Treatment with NOXAP should not be stopped abruptly, but rather reduced slowly to allow the lungs to adapt to the normal oxygen concentration in the air.

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

4. Possible side effects

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

Your doctor will observe and closely monitor any side effects. It is unlikely that you will suffer from these side effects.

Blood and lymphatic system disorders

• An increase in the concentration of nitric oxide in the blood may carry the risk of methemoglobinemia. In this case, the ability of the blood to transport oxygen may decrease. If this occurs, your doctor will immediately decrease the dosage of nitric oxide, to allow the blood to reach its normal oxygen transport capacity. In pediatric patients and others with reduced levels of the enzyme methemoglobin reductase, this risk may increase. The formation of methemoglobin with a serum level of > 5% with concentrations of inhaled nitric oxide of <20 ppm is very rare (< 1 10,000).< li>
• Bleeding time:In a preclinical study, it has been observed that inhaled nitric oxide increases bleeding time. However, in controlled clinical studies, no significant differences have been found between the test group and the treatment group regarding hemorrhagic complications.

General disorders and administration site conditions

• A lack of responseto treatment may be observed in 30 to 45% of cases.
• A significant increase in NO2 concentrations at low therapeutic doses (<20 ppm) of inhaled no, with evidence clinical toxicity due to no2, is a very rare complication (< 1 10,000).< li>
• The abrupt interruption of treatment with inhaled nitric oxide frequently (> 1/10) causes rebound reactions with an intensification of pulmonary vasoconstriction and hypoxemia.

Reporting of side effects

If you experience any side effects, ask your doctor or pharmacist, even if they are not listed in this package leaflet. You can also report them directly through the Spanish Medicines Agency's website: www.notificaRAM.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of NOXAP

Keep out of the reach and sight of children.

Do not use NOXAPafter the expiry date stated on the label, after “EXP”.

All regulations regarding the handling of pressure vessels must be followed.

Storage is supervised by local hospital specialists. The vessels must be stored in well-ventilated rooms or covered, ventilated areas, protected from rain and direct sunlight.

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

Storage in the pharmacy department

The vessels must be stored in a designated area exclusively for the storage of medicinal gases, which is well-ventilated, clean, and locked. This area must have a separate and special place for the storage of nitric oxide vessels.

Storage in the medical department

The vessels must be kept in a place with the necessary equipment to ensure they remain in a vertical position.

6. Contents of the pack and further information

Composition of NOXAP

NOXAP is a gas mixture.

• The active substance is: nitric oxide 800 ppm (mol/mol)
• The other component is: nitrogen.

Appearance and pack contents

NOXAP is a compressed medicinal gas.

NOXAP is stored in high-pressure vessels made of aluminum or aluminum with an external layer of elastomers. The valves that close the vessels are made of steel. The vessel sizes are 2 L, 5 L, 10 L, 20 L, and 40 L.

NOXAP is filled as a gas in these gas cylinders at a pressure of 200 bar. Not all sizes are marketed.

The package color code is turquoise blue and white body.

Marketing authorization holder

SE. Carburos Metálicos, S.A.

Avda de la Fama 1, 08940 – Cornella de Llobregat

Manufacturer:

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

Belgium: NOXAP 800ppm mol/mol, medicinal gas, compressed

Netherlands: NOXAP 800ppm mol/mol, medicinal gas, compressed

France: NOXAP 800 ppm mol/mol, medicinal gas, compressed

Portugal: NOXAP 800 ppm mol/mol, medicinal gas, compressed

Czech Republic: NOXAP 800 ppm mol/mol, medicinal gas, compressed

Germany: NOXAP 800 ppm Mol/Mol Gas zur medizinischen Anwendung, druckverdichtet

Spain: NOXAP 800 ppm mol/mol, medicinal gas, compressed

Poland: NOXAP 800 ppm mol/mol, medicinal gas, compressed

Italy: NOXAP 800 ppm mol/mol, medicinal gas, compressed

This package leaflet was approved inJanuary 2020.

Detailed information on this medicine is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es.