Prospect: information for the user

NOXAP 800 ppm mol/mol, medicinal gas, compressed tablet

Nitric oxide

Read this prospect thoroughly 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 pharmacist.
• If you experience adverse effects, consult your doctor or pharmacist, even if they are not listed in this prospect. See section 4.

1. What is NOXAP and what is it used for

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

3. How to use NOXAP

4. Possible adverse effects

5. Storage of NOXAP

6. Contents of the package and additional information

NOXAP is a gas mixture for inhalation use.

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

What are its uses?

NOXAP must be administered exclusively by healthcare professionals and is only for strictly hospital use. NOXAP is indicated in the following cases:

In newborns with a lack of oxygen in the blood (hypoxemic respiratory insufficiency) 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.

Do not take NOXAP in the following cases:

• Infants with confirmed right-to-left shunt or significant left-to-right shunt.
• Patients with congenital or acquired deficiency of methemoglobin reductase (MetHb reductase) or glucose 6 phosphate dehydrogenase (G6PD).

Be cautious with 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 medications

Inform your doctor if you are using or have recently used other medications, 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 must be performed during treatment with NOXAP.

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

Medications that increase methemoglobin concentrations: When medications such as alkyl nitrates, sulfonamides, and prilocaine are administered with nitric oxide, there is an increased risk of presenting 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 observed interactions.

The doctor will decide if NOXAP can be used with other medications and closely monitor treatment.

Pregnancy and breastfeeding

NOXAP should not be used during pregnancyunless the patient's clinical condition requires treatment with NOXAP.

Adverse effects may be expected since methemoglobin is considered harmful to the fetus and nitric oxide has demonstrated a genotoxic potential by inducing structural alterations in DNA.

Breastfeeding should be discontinued during treatment with NOXAP.

Driving and operating machinery

No studies have been reported on the ability to drive and operate machinery.

NOXAP must be administered exclusively by healthcare professionals and is only for strictly hospital use.

NOXAP is administered via 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. Your doctor will then reduce or stop the administration of NOXAP and subsequently determine the most suitable treatment to follow.

If you interrupt treatment with NOXAP

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

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

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

Like all medications, NOXAP may have adverse effects, although not everyone will experience them.

Your doctor will closely monitor and watch for any adverse effects. It is unlikely that you will suffer from these adverse effects.

Blood and Lymphatic System Disorders

• An increase in nitric oxide concentration in the blood may lead to the risk of developing methemoglobinemia. In this case, the blood's ability to transport oxygen may decrease. If this occurs, your doctor will immediately reduce the dosage of nitric oxide to allow the blood to regain its normal oxygen transport capacity. In pediatric patients and others with reduced levels of the methemoglobin reductase enzyme, this risk may increase. The formation of methemoglobin with a serum level of > 5% with inhaled nitric oxide concentrations of <20>1/10,000).
• Bleeding Time:In a preclinical study, inhaled nitric oxide was observed to increase bleeding time. However, in controlled clinical studies that have been conducted, no significant differences were found between the control group and the treatment group in terms of hemorrhagic complications.

General Disorders and Administration Site Conditions

• Alack of responseto treatment may be observed in 30 to 45% of cases.
• A significant increase in NO2concentrations at therapeutic doses of <20 ppm) of inhaled NO, with evidence of clinical toxicity by NO2, is a very rare complication (<1/10,000).
• Abrupt interruption of treatment with inhaled nitric oxide causes frequent (>1/10) rapid rebound reactions that present an intensification of pulmonary vasoconstriction and hypoxemia.

Reporting Adverse Effects

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it is an adverse effect that does not appear in this prospectus. You can also report them directly through 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 on the safety of this medication.

Keep out of reach and sight of children.

Do not useNOXAPafter the expiration date appearing on the label of the container, after “CAD”.

All regulations related to the handling of pressurized containers must be followed.

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

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

Conservation in the pharmacy department

Containers must be stored in a designated area exclusively for the storage of medical gases, which must be well-ventilated, clean, and locked with a key. This area must have a separate and special place for the storage of nitric oxide containers.

Conservation in the medical department

Containers must be stored in a place with the necessary equipment to ensure they remain in an upright position.

Composition of NOXAP

NOXAP is a combination of gases.

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

Appearance of the product and contents of the container

NOXAP is a compressed medicinal gas.

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

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

The container color code is turquoise ojiva blue and white body.

Holder of the marketing authorization

SE. Carburos Metálicos, S.A.

Address:

Avda de la Fama 1, 08940 – Cornella de Llobregat

Manufacturer:

This medicine is authorized in the member states of the European Economic Area with the following names:

Bélgica: NOXAP800ppm mol/mol, medicinaal gas, samengeperst

Países Bajos: NOXAP800ppm mol/mol, medicinaal gas, samengeperst

Francia: NOXAP800 ppm mol/mol, gaz médicinal comprimé

Portugal: NOXAP 800 ppm mol/mol, gás medicinal comprimido

República Checa: NOXAP800 ppm mol/mol, medicinálníplyn, stlacený

Alemania: NOXAP800 ppm Mol/MolGas zur medizinischen Anwendung, druckverdichtet

España: NOXAP800 ppm mol/molgas medicinal comprimido

Polonia: NOXAP800ppm mol/mol, gaz medyczny, sprezony

Italia: NOXAP800ppm mol/mol, gas medicinale compresso

This leaflet was approved inJanuary 2020.

The detailed information of this medicine is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS) http:// www.aemps.gob.es.