Noxap

Package leaflet: Information for the user

NOXAP, 800 ppm mol/mol, medicinal gas, compressed
Nitrous oxide
Please read all of this leaflet carefully before use, as it contains important information for the patient.

• Keep this leaflet, so that you can read it again if necessary.
• If you have any questions, please consult your doctor or pharmacist.
• If you experience any adverse reactions, including any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of the leaflet

1. What Noxap is and what it is used for
2. Important information before using Noxap
3. How to use Noxap
4. Possible side effects
5. How to store Noxap
6. Contents of the package and other information

1. What Noxap is and what it is used for

Noxap is a medicinal gas mixture for inhalation.
Noxap is a compressed medicinal gas, consisting of a gas mixture containing nitrous oxide at a concentration of 800 ppm mol/mol.
Uses
Noxap must be administered only by a healthcare professional and is intended solely for use in hospital settings. Noxap is indicated in the following cases:

1. In newborns with low blood oxygen levels (hypoxic respiratory failure) caused by various conditions. Noxap improves blood oxygenation and reduces the need for extracorporeal membrane oxygenation (ECMO).
2. In adult and pediatric patients undergoing heart surgery with acute pulmonary hypertension. Noxap reduces abnormally high blood pressure in the lungs and decreases the risk of right heart failure.

2. Important information before using Noxap

When not to use Noxap:

• in newborns diagnosed with right-to-left shunt or significant left-to-right shunt;
• in patients with congenital or acquired deficiency of methemoglobin reductase (MetHb) or glucose-6-phosphate dehydrogenase (G6PD).

Precautions for Noxap:

• In patients with left ventricular dysfunction, Noxap may lead to heart failure and pulmonary edema.
• Exercise caution in patients with complex congenital heart defects.

Cases of pulmonary fluid retention associated with nitric oxide use have been reported in patients with disease caused by blockage or narrowing of pulmonary veins. If a patient (adult or child) develops shortness of breath or difficulty breathing, contact a physician immediately.

Noxap and other medicines

Inform the physician about all medicines currently used or recently used by the patient, including those available without a prescription.

• Oxygen: in the presence of oxygen, nitric oxide is rapidly oxidized, forming substances toxic to the lungs. To avoid this situation, treatment with Noxap must be continuously monitored.
• Nitric oxide donors: cardiovascular drugs such as sodium nitroprusside and nitroglycerin may enhance the effect of Noxap, increasing the risk of methemoglobinemia.
• Drugs increasing methemoglobin levels: concomitant administration of drugs such as alkyl nitrates, sulfonamides, and prilocaine with nitric oxide increases the risk of methemoglobinemia.
• Synergistic effects have been observed when administered simultaneously with vasoconstrictive agents (almitrine, phenylephrine), prostacyclins, and phosphodiesterase inhibitors; however, without increased incidence of adverse effects.
• Inhaled nitric oxide has been used concomitantly with tolazoline, dopamine, dobutamine, norepinephrine, corticosteroids, and surfactants without observable drug interactions.

The physician will decide whether Noxap can be used with other medicines and will carefully monitor the course of treatment.

Pregnancy and breastfeeding

Noxap medicinal product 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 hazardous to the fetus, and nitric oxide has demonstrated genotoxic potential, as it causes structural DNA changes.

Breastfeeding must be discontinued during treatment with Noxap.

Driving and operating machinery

There are no reports regarding harmful effects on the ability to drive or operate machinery.

3. How to use Noxap

Noxap must be administered only by a healthcare professional and is intended for use in a hospital setting.
Noxap is delivered by inhalation using a delivery system that administers the prescribed concentration of nitric oxide to the lungs by diluting Noxap in a mixture of oxygen and air.
The dose and duration of treatment with Noxap will be determined by the physician.
Administration of a higher than recommended dose of Noxap will trigger an alarm signal in the drug delivery system. The physician will then reduce the dose or discontinue administration of Noxap and determine the most appropriate course of further treatment.
Discontinuation of Noxap treatment
The physician will gradually reduce the Noxap dose towards the end of treatment.
Noxap administration should not be abruptly stopped; the dose should be slowly tapered 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 medicine, consult your doctor or another healthcare professional.

4. Possible adverse reactions

Like all medicines, Noxap can cause adverse reactions, although they do not occur in everyone.
The doctor will closely monitor the treatment to detect any adverse reactions. It is unlikely
that the patient will notice these adverse reactions themselves.
Blood system disorders

• Increased blood levels of nitric oxide may increase the risk of developing methemoglobinemia. In such a case, the ability of blood to deliver oxygen may be impaired. If this occurs, the doctor will immediately reduce the dose of nitric oxide to restore the blood's normal oxygen-carrying capacity. This risk may be higher in children and in individuals with reduced methemoglobin reductase enzyme activity. Serum methemoglobin concentration exceeding 5% during inhalation of nitric oxide at concentrations < 20 ppm is very rare (may occur in fewer than 1 in 10,000 people).
• Bleeding time: Preclinical studies have shown that nitric oxide inhalation prolongs bleeding time. However, controlled clinical trials have not confirmed a significant difference in hemorrhagic complications between the treated group and the control group.

General disorders and administration site conditions

• Lack of response to treatment is observed in 30–45% of cases. A significant increase in NO concentration at low therapeutic doses (< 20 ppm) administered via NO inhalation, as well as clinical signs of NO toxicity, are very rare complications (may occur in fewer than 1 in 10,000 people).
• Abrupt discontinuation of inhaled nitric oxide therapy very commonly leads (may occur in more than 1 in 10 people) to a rapid rebound reaction, manifested by severe pulmonary vasoconstriction and hypoxemia.

If any of the adverse symptoms worsen or if any adverse symptoms not listed in this leaflet occur,
the patient should inform their doctor or other healthcare professional.
Reporting of adverse reactions
If any adverse reactions occur, including those not listed in this leaflet, the patient should inform their doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products:
Al. Jerozolimskie 181C
02-222 Warsaw
Phone: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorization holder.
Reporting adverse reactions helps to gather more information on the safety of the medicine.

5. How to store the medicinal product Noxap

The medicinal product should be stored in a place inaccessible and not visible to children.
Do not use Noxap after the expiry date indicated on the gas cylinder label following the abbreviation "EXP".
All regulations concerning the handling of compressed gas cylinders must be observed.
Store under the supervision of a specialist employed by the hospital. Gas cylinders must be stored in well-ventilated areas or ventilated storage rooms, protected from rain and direct sunlight.
Protect gas cylinders from shocks, falls, oxidizing or flammable materials, moisture, and sources of heat or ignition.

Storage in the pharmaceutical department
Gas cylinders must be stored in a location designated exclusively for the storage of medical gases, which is well-ventilated, clean, and secured with a lock. A separate room should be available at this location for the storage of nitrous oxide cylinders.

Storage in the medical department
Gas cylinders must be stored in an area equipped appropriately to ensure that cylinders remain in an upright position.

6. Contents of the package and other information

What Noxap contains
Noxap is a mixture of gases.

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

What Noxap looks like and contents of the pack
Noxap is a compressed medical gas.
Noxap is stored in high-pressure gas cylinders made of aluminum or aluminum with an outer layer of elastomers. The cylinder valves are made of stainless steel. Gas cylinders are available in sizes of 2 l, 5 l, 10 l, 20 l, and 40 l.
The cylinders are filled with Noxap at a pressure of 200 bar. Not all pack sizes may be marketed.

Gas cylinders have color markings: the shoulder is turquoise-blue and the body is white.
Marketing Authorisation Holder:
Air Products Sp. z o.o.
ul. Komitetu Obrony Robotników 48
02-146 Warsaw
Manufacturer:
S.E. de CARBUROS METÁLICOS S.A.
Poligono Nordeste, C-35 km 59
08470 Sant Celoni (Barcelona)
Spain
This medicinal product is authorised for marketing in the European Economic Area countries under the following names:
Belgium: Noxap 800 ppm mol/mol, medicinaal gas, samengeperst
Netherlands: Noxap 800 ppm mol/mol, medicinaal gas, samengeperst
France: Noxap 800 ppm mol/mol, gaz médicinal comprimé
Portugal: Noxap 800 ppm mol/mol, gás medicinal comprimido
Czech Republic: Noxap 800 ppm mol/mol, medicinální plyn, stlačený
Germany: Noxap 800 ppm Mol/Mol Gas zur medizinischen Anwendung, druckverdichtet
Spain: Noxap 800 ppm moles/mole, gas medicinal comprimido
Italy: NOXAP 800 ppm mol/mol, gas medicinale compresso