Noxap

Leaflet attached to the packaging: information for the user

NOXAP, 200 ppm mol/mol, medical gas, compressed

Nitric oxide

You should carefully read the contents of the leaflet before using the medicine, as it contains important information for the patient.

• -You should keep this leaflet, so that you can read it again if you need to.
• In case of any doubts, you should consult a doctor or pharmacist.
• If the patient experiences any adverse reactions, including any adverse reactions not listed in this leaflet, they should inform their doctor or pharmacist. See section 4.

Table of contents of the leaflet

• 1. What is Noxap and what is it 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 packaging and other information

1. What is Noxap and what is it used for

Noxap is a mixture of gases for inhalation.
Noxap is a compressed medical gas, which is a mixture of gases containing nitric oxide
at a concentration of 200 ppm mol/mol.
Indications
Noxap can only be administered by a healthcare professional and is intended
for use in hospital settings. The use of Noxap is indicated in the following
cases:

• 1. In newborns with oxygen deficiency in the blood(hypoxemic respiratory failure) caused by various factors. Noxap improves blood oxygenation and reduces the need for extracorporeal circulation.
• 2. In adult and pediatric patients undergoing cardiac surgery with acute pulmonary hypertension. Noxap lowers high blood pressure in the lungs and reduces the risk of right heart failure.

2. Important information before using Noxap

When not to use Noxap:

• in newborns with diagnosed left-to-right or significant right-to-left shunt;
• in patients with congenital or acquired methemoglobin reductase deficiency (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.
• Care should be taken in patients with complex, congenital heart defects.

There have been reports of fluid retention in the lungs associated with the use of nitric oxide 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, they should immediately contact their
doctor.

Noxap and other medicines

You should tell your doctor about all medicines that the patient is currently taking or has recently taken,
including those that are available without a prescription.

• Oxygen: in the presence of oxygen, nitric oxide rapidly oxidizes to form toxic substances for the lungs. To avoid this situation, the treatment with Noxap should be constantly monitored.
• Nitric oxide donors: cardiovascular drugs, such as sodium nitroprusside and nitroglycerin, may enhance the effect of Noxap, increasing the risk of methemoglobinemia.
• Methemoglobin-increasing drugs: co-administration of nitric oxide with drugs such as alkyl nitrates, sulfonamides, and prilocaine increases the risk of methemoglobinemia.
• Synergistic effects have been observed when administered concomitantly with drugs that cause vasoconstriction (almitrine, phenylephrine), prostacyclins, and phosphodiesterase inhibitors, but without exacerbating adverse reactions.
• Nitric oxide for inhalation has been used concomitantly with tolazoline, dopamine, dobutamine, norepinephrine, steroid drugs, and surfactants, without observed drug interactions.

The doctor will decide whether it is possible to use Noxap with other medicines and will closely
monitor the course of treatment.

Pregnancy and breastfeeding

Noxap should not be used during pregnancy, unless the woman's clinical condition requires
treatment with Noxap.
Harmful effects can be expected, as methemoglobin is considered hazardous to the fetus, and nitric oxide has shown genotoxic potential, causing structural changes in DNA.
During treatment with Noxap, breastfeeding should be discontinued.

Driving and operating machinery

There are no reports of a harmful effect on the ability to drive vehicles and operate machinery.

3. How to use Noxap

Noxap must be administered only by a healthcare professional and is intended
for use in hospital settings.
Noxap is administered by inhalation using a delivery system that delivers 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 are determined by the doctor.
Using a higher dose of Noxap than recommendedwill trigger an alarm signal
in the delivery system. The doctor will then reduce the dose or discontinue Noxap and determine the most appropriate method of further treatment.

Discontinuation of Noxap

The doctor will gradually reduce the dose of Noxap at the end of treatment.
Noxap should not be abruptly discontinued, but rather the dose should be gradually reduced, so that the lungs can adapt to the normal oxygen concentration in the air.
In case of any further doubts related to the use of the medicine, you should consult a doctor or another healthcare professional.

4. Possible side effects

Like all medicines, Noxap can cause side effects, although not everybody gets them.
The doctor will closely monitor the treatment to detect any side effects. It is unlikely that the patient will notice these side effects.

Cardiovascular disorders

• -Elevated nitric oxide levels in the blood may increase the risk of methemoglobinemia. In such a case, the ability to deliver oxygen with the blood may be impaired. If this happens, the doctor will immediately reduce the dose of nitric oxide to restore the normal ability of the blood to transport oxygen. This risk may be higher in children and individuals with reduced methemoglobin reductase enzyme activity. The occurrence of methemoglobin levels in serum above 5% during inhalation of nitric oxide at concentrations below 20 ppm is very rare (may occur less frequently than 1 in 10,000 people).
• -Bleeding time:preclinical studies have shown that inhalation of nitric oxide prolongs bleeding time. However, clinical trials with a control group did not confirm a significant difference in the incidence of bleeding complications between the treated group and the control group.

General disorders and administration site conditions

• Lack of response to treatmentis observed in 30-45% of cases.
• Significant elevation of NO levels at low therapeutic doses (<20 ppm) of inhaled no, as well symptoms clinical no toxicity, are very rare (may occur less frequently than 1 in 10,000 people) complications.< li>
• Abrupt discontinuation of inhaled nitric oxide therapy often (may occur more frequently than 1 in 10 people) leads to a rapid rebound reaction, characterized by severe pulmonary vasoconstriction and hypoxemia.

If the patient experiences any worsening of side effects or any side effects not listed in the leaflet, they should inform their doctor or another healthcare professional.

Reporting side effects

If any side effects occur, including any side effects not listed in the leaflet, you should inform your doctor or pharmacist. Side effects can be reported directly to the Department of Monitoring of Adverse Reactions to Medicinal Products 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
Side effects can also be reported to the marketing authorization holder.
By reporting side effects, you can help provide more information on the safety of the medicine.

5. How to store Noxap

The medicine should be stored out of sight and reach of children.
Noxap should not be used after the expiry date stated on the label of the gas cylinder after the abbreviation "EXP".
All regulations regarding the handling of gas cylinders should be followed.
Store under the supervision of a specialist employed by the hospital. Gas cylinders should be stored in well-ventilated rooms or ventilated warehouses, protected from rain and direct sunlight.
Protect gas cylinders from shocks, falls, oxidizing materials or flammable materials, moisture, and heat or ignition sources.
Storage in the pharmaceutical department
Gas cylinders should be stored in a place designated exclusively for the storage of medical gases, which is well-ventilated, clean, and locked. This place should have a separate room for storing nitric oxide cylinders.
Storage in the medical department
Gas cylinders should be stored in a place where there is appropriate equipment, ensuring that the cylinders remain in a vertical position.

6. Contents of the packaging and other information

What Noxap contains

Noxap is a mixture of gases.

• The active substance is: nitric oxide at a concentration of 200 ppm (mol/mol).
• The other ingredient is: nitrogen.

What Noxap looks like and what the packaging contains

Noxap is a medical gas, compressed.
Noxap is stored in gas cylinders under high pressure, made of aluminum or aluminum with an outer layer of elastomers. The valves of the gas cylinders 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 under a pressure of 200 bar. Not all pack sizes may be marketed.
Gas cylinders have color coding: the cylinder head is turquoise-blue and the body is white.

Marketing authorization 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 authorized in the Member States of the European

Economic Area 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

Date of last revision of the leaflet: 18/02/2025