Noxap

Package leaflet: Information for the user

NOXAP, 200 ppm mol/mol, medicinal gas, compressed
Nitric oxide
Please read all of this leaflet carefully before use, as it contains important information for the patient.

• Keep this leaflet, as you may need to read it again.
• If you have any further questions, please consult your doctor or pharmacist.
• If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor or pharmacist immediately. 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 pack and other information

1. What Noxap is and what it is used for

Noxap is a gas mixture for inhalation.
Noxap is a compressed medicinal gas consisting of a gas mixture containing nitric oxide at a concentration of 200 ppm mol/mol.
Indications
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 cardiac 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 with 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 accumulation associated with nitric oxide use have been reported in patients with disease caused by blockage or narrowing of the pulmonary veins. If a patient (adult or child) experiences shortness of breath or difficulty breathing, contact a doctor immediately.

Noxap and other medicines

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

• Oxygen: in the presence of oxygen, nitric oxide is rapidly oxidized, forming substances toxic to the lungs. To avoid this, 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.
• Medicines 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 concurrently with tolazoline, dopamine, dobutamine, norepinephrine, steroid medicines, and surfactants without observable drug interactions.

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

Pregnancy and breastfeeding

Noxap should not be used during pregnancy unless the clinical condition of the woman requires treatment with Noxap.

Harmful effects may be expected, since methemoglobin is considered hazardous to the fetus, and nitric oxide has demonstrated genotoxic potential, causing 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 supplies 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 further treatment approach.
Discontinuation of Noxap treatment
Towards the end of treatment, the physician will gradually reduce the dose of Noxap.
Noxap should not be discontinued abruptly; 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 regarding the use of this medicine, consult your doctor or another healthcare professional.

4. Possible adverse reactions

Like any medicine, Noxap may cause adverse reactions, although not everyone experiences them.
The doctor will closely monitor the treatment to detect any adverse reactions. It is unlikely
that the patient will observe 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 promptly reduce the dose of nitric oxide to restore normal oxygen-carrying capacity of the blood. This risk may be higher in children and individuals with reduced methemoglobin reductase enzyme activity. Serum methemoglobin concentration exceeding 5% during nitric oxide inhalation at concentrations < 20 ppm is very rare (may occur in fewer than 1 in 10,000 people).
• Bleeding time: Preclinical studies have shown that inhalation of nitric oxide prolongs bleeding time. However, controlled clinical trials have not confirmed a significant difference in the occurrence of 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.
• Significant increase in NO concentration at low therapeutic doses (< 20 ppm) administered by NO inhalation, as well as clinical NO toxicity symptoms, 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 pronounced pulmonary vasoconstriction and hypoxemia.

If any of the adverse symptoms worsen or if any adverse reactions not listed in the 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 for Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products:
Al. Jerozolimskie 181C
02-222 Warsaw
Tel.: + 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 allows the collection of additional information on the safety of the medicine.

5. How to store the medicinal product Noxap

The medicinal product must be stored in a place inaccessible and not visible to children.
Do not use Noxap after the expiry date stated on the gas cylinder label following the abbreviation "EXP".
All regulations concerning the handling of compressed gas cylinders must be observed.
The cylinders must be stored under the supervision of a specialist employed by the respective hospital. Gas cylinders must be stored in well-ventilated rooms or ventilated storage areas, 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 locked. A separate room within this location must be designated for the storage of nitrous oxide cylinders.

Storage in the medical department
Gas cylinders must be stored in an area equipped with appropriate devices ensuring that the cylinders remain in an upright position.

6. Contents of the pack and other information

What Noxap contains
Noxap is a gas mixture.

• The active substance is: nitric oxide at a concentration of 200 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.
Gas cylinders are filled with Noxap at a pressure of 200 bar. Not all pack sizes may be marketed.

Gas cylinders have colour markings: the shoulder of the cylinder 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 supply in the European Economic Area member states under the following names:
Belgium: Noxap 200 ppm mol/mol, medicinaal gas, samengeperst
Netherlands: Noxap 200 ppm 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, stlačený
Germany: Noxap 200 ppm Mol/Mol Gas zur medizinischen Anwendung, druckverdichtet
Spain: Noxap 200 ppm moles/mole, gas medicinal comprimido
Italy: NOXAP 200 ppm mol/mol, gas medicinale compresso