Noxap 800 ppm mol/mol, compressed medicinal gas

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

NOXAP 800 ppm mol/mol, medicinal gas, compressed

Nitric oxide

Read the entire 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 doctor or pharmacist.
• If you experience any side effects, consult your doctor or pharmacist, even if they are side effects not listed in this leaflet. See section 4.

Leaflet contents

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

1. What NOXAP is and what it is used for

NOXAP is a gas mixture for inhalation use.

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

What is it used for?

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

In newborns with low blood oxygen (hypoxemic respiratory failure) due to various causes.

NOXAP improves oxygenation and reduces the need for extracorporeal circulation.

In pediatric and adult patients undergoing cardiac surgery with acute pulmonary arterial hypertension (pulmonary hypertension). NOXAP reduces pulmonary hypertension and the risk of right heart failure.

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

Do not take NOXAP in the following cases:

• Newborns with proven dependence on right-to-left shunting of blood or who suffer significant left-to-right shunting.
• Patients with congenital or acquired deficiency of methemoglobin reductase (MetHb reductase) or glucose-6-phosphate dehydrogenase (G6PD).

Exercise special caution with NOXAP:

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

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

Use of other medicines

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

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

Drugs that increase methemoglobin levels: When drugs such as alkyl nitrates, sulfonamides, and prilocaine are administered together with nitric oxide, the risk of methemoglobinemia increases.

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 concomitantly with tolazoline, dopamine, dobutamine, norepinephrine, steroids, and surfactants, without observed interactions.

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

Pregnancy and breastfeeding

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

Harmful effects may be expected, as methemoglobin is considered harmful to the fetus and nitric oxide has demonstrated genotoxic potential by inducing structural DNA alterations.

Breastfeeding must be interrupted during treatment with NOXAP.

Driving and use of machines

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

3. How to use NOXAP

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

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

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

If you receive more NOXAP than you should, the delivery system will activate a warning signal. Then, your doctor will reduce or stop the administration of NOXAP and subsequently determine the most appropriate course of action.

If treatment with NOXAP is interrupted

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

Treatment with NOXAP must not be stopped abruptly, but rather tapered 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 adverse effects

Like all medicines, NOXAP may have adverse effects, although not everyone experiences them.

Your doctor will closely observe and monitor for any adverse effects. It is unlikely that you will experience these adverse effects.

Disorders of the blood and lymphatic system

• An increase in nitric oxide concentration in the blood may lead to the risk of methemoglobinemia. In this case, the blood's oxygen-carrying capacity may decrease. If this occurs, your doctor will immediately reduce the nitric oxide dosage to allow the blood to return to its normal oxygen-carrying capacity. This risk may be increased in pediatric patients and others with reduced levels of the enzyme methemoglobin reductase. Formation of methemoglobin with serum levels > 5% at inhaled nitric oxide concentrations < 20 ppm is very rare (< 1/10,000).
• Bleeding time: In a preclinical study, inhaled nitric oxide was observed to increase bleeding time. However, in controlled clinical studies, no significant differences were found between the control group and the treatment group regarding hemorrhagic complications.

General disorders and administration site reactions

• A lack of response to 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 of clinical toxicity due to NO2, is a very rare complication (< 1/10,000).
• Abrupt discontinuation of inhaled nitric oxide treatment frequently causes (> 1/10) rapid rebound reactions characterized by intensification of pulmonary vasoconstriction and hypoxemia.

Reporting of adverse effects

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it is an adverse effect not listed in this leaflet. You may also report them directly through the Spanish Pharmacovigilance System for Human Medicinal Products: www.notificaRAM.es. By reporting adverse 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 NOXAP after the expiry date stated on the container label, following “EXP”.

All regulations relating to the handling of pressurized containers must be observed.

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

Protect containers from impact, falls, oxidizing materials, flammable substances, moisture, heat sources, and ignition sources.

Storage in the pharmacy department

Containers must be stored in a designated area exclusively intended for the storage of medicinal gases, which must be well-ventilated, clean, and secured with a lock. This area must include a separate, dedicated space for the storage of nitric oxide containers.

Storage in the medical department

Containers must be stored in an area equipped appropriately to ensure they remain in an upright position.

6. Contents of the container and other information

Composition of NOXAP

NOXAP is a combination of gases.

• The active substance is: nitric oxide 200 ppm (mol/mol)
• The other component is: nitrogen.

Appearance of the medicinal 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 outer layer of elastomers. The valves sealing 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 into these gas cylinders at a pressure of 200 bar. Not all container sizes are marketed.

The color code of the packaging is turquoise bullet and white body.

Marketing Authorization Holder

S.E. de Carburos Metálicos, S.A.

Avda. de la Fama, 1

08940-Cornellà de Llobregat

Spain

Manufacturer:

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

Belgium: NOXAP 200ppm mol/mol, medicinaal gas, samengeperst

Netherlands: NOXAP 200ppm mol/mol, medicinaal gas, samengeperst

France: NOXAP 200 ppm mol/mol, gaz médicinal comprimé

Portugal: NOXAP 200 ppm mol/mol, gás medicinal comprimido

Czech Republic: NOXAP 200 ppm mol/mol, medicinální plyn, stlacený

Germany: NOXAP 200 ppm Mol/Mol Gas zur medizinischen Anwendung, druckverdichtet

Spain: NOXAP 200 ppm mol/mol gas medicinal comprimido

Poland: NOXAP 200 ppm mol/mol, gaz medyczny, sprezony

Italy: NOXAP 200 ppm mol/mol, gas medicinale compresso

This patient information leaflet was approved in January 2025