NOXAP 200 PPM Inhalation gas

Зміст інструкції

1. NOXAP 200 ppm mol/mol, compressed medicinal gas
   1. What is NOXAP and what is it used for
   2. What you need to know 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
2. NOXAP 800 ppm mol/mol, compressed medicinal gas
   1. What is NOXAP and what is it used for
   2. What you need to know 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

NOXAP 200 ppm mol/mol, compressed medicinal gas

nitric oxide

Read this leaflet carefully before using this medicine as it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• - If any side effects occur, including those not listed in this leaflet, ask your doctor or pharmacist. See section 4.

Contents of this leaflet:

• 1. What NOXAP is and what it is used for
• 2. What you need to know 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 is NOXAP and what is it used for

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

How is it used?
NOXAP must be administered exclusively by healthcare professionals and is reserved
exclusively for hospital use. NOXAP is indicated in the following conditions:

• 1. In newborns with oxygen deficiency in the blood(hypoxemic respiratory failure) due to various causes. NOXAP improves oxygenation and reduces the need for extracorporeal circulation.
• 2. In pediatric and adult patients undergoing cardiac surgery with acute pulmonary hypertension(pulmonary hypertension). NOXAPreduces pulmonary hypertension and the risk of right heart failure.

2. What you need to know before using NOXAP

Do not use NOXAP in the following cases:

• Newborns with documented tendency to right-to-left shunt or affected by significant left-to-right shunt.
• Patients with congenital or acquired deficiency of methemoglobin reductase (MetHb reductase) or glucose-6-phosphate dehydrogenase (G6PD).

Take special care with NOXAP:

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

Use of other medicines
Tell your doctor if you are taking or have recently taken any other medicines, including those
obtained without a prescription.

• Oxygen: in the presence of oxygen, nitric oxide rapidly oxidizes producing substances that are toxic to the lungs. To avoid this situation, treatment with NOXAP is accompanied by continuous monitoring.
• NO donors: some cardiological medicines, such as sodium nitroprusside and nitroglycerin, may have an additive effect with NOXAP, increasing the risk of methemoglobinemia.
• Drugs that increase methemoglobin concentrations: when alkyl nitrates, sulfonamides and prilocaine are administered together with nitric oxide, there is an increased risk of methemoglobinemia.
• With the administration of vasoconstrictors (almitrine, phenylephrine), prostacyclin and phosphodiesterase inhibitors, synergistic effects have been reported, but without an increase in adverse events.
• Inhaled nitric oxide has been used simultaneously with tolazoline, dopamine, dobutamine, norepinephrine, steroids and surfactants, without observing pharmacological interactions.

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

Pregnancy and breastfeeding
NOXAP should not be used during pregnancy unless the clinical conditions of the women
require treatment with NOXAP.
Harmful effects are predictable as methemoglobin is considered harmful to the fetus, and nitric oxide has shown a genotoxic potential given by the induction of structural alterations of DNA.
During treatment with NOXAP, breastfeeding must be discontinued.

Driving and operating machinery
No adverse events related to the ability to drive vehicles and operate machinery have been reported.

3. How to use NOXAP

NOXAP must be administered exclusively by healthcare professionals and is reserved
exclusively for hospital use.
NOXAP is administered by inhalation through a system that delivers the
prescribed nitric oxide concentration to the lungs, diluting NOXAP in a mixture of oxygen and air.
The doctor will determine the dosage and duration of treatment with NOXAP.

If you receive more NOXAP than you should, the delivery system will activate an alarm signal. At
that point, the doctor will reduce or stop the administration of NOXAP, then establish the
most appropriate treatment to follow.

If you stop receiving NOXAP
Towards the end of treatment, the doctor will gradually reduce the dosage of NOXAP.
Treatment with NOXAP should not be stopped abruptly, but gradually reduced in
order to allow the lungs to adapt to the normal oxygen concentration in the air.
If you have any doubts about the use of this medicine, ask your doctor or other healthcare professionals.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone will experience them.
The doctor will report and closely monitor any side effects. It is unlikely that you will be able to ascertain these side effects on your own.

Blood and lymphatic system disorders

• An elevated concentration of nitric oxide in the blood may determine a risk of methemoglobinemia. In this case, the blood's ability to transport oxygen may be reduced. If this occurs, the doctor will immediately reduce the dosage of nitric oxide to allow the blood to recover its normal oxygen-carrying capacity. In pediatric patients and other subjects with reduced levels of the methemoglobin reductase enzyme, this risk may increase. The formation of methemoglobin at serum levels > 5% with inhaled nitric oxide at concentrations < 20 ppm is very rare (may affect up to 1 in
• 10,000).
• Bleeding time: a preclinical study revealed that inhaled nitric oxide increases bleeding time. However, controlled clinical studies have not shown significant differences between the control group and the treatment group regarding hemorrhagic complications.

Systemic disorders and conditions related to the site of administration

• In 30-45% of cases, a lack of response to treatment may be observed.
• Significant increases in NO levels with low therapeutic doses (< 20 ppm) of inhaled NO, as well as evidence of clinical NO toxicity, are a very rare complication (may affect up to 1 in 10,000).
• Abrupt discontinuation of inhaled nitric oxide therapy very often causes (very common frequency: may affect more than rapid rebound reactions characterized by intense pulmonary vasoconstriction and hypoxemia.

If any side effect worsens, or if you notice any side effects not listed in this leaflet,
consult your doctor or other healthcare professionals.

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, consult your
doctor or pharmacist. You can also report side effects directly through the national reporting system at
https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects, you can help provide more information on the safety of
this medicine.

5. How to store NOXAP

Keep out of the sight and reach of children.
Do not use NOXAP after the expiry date which is reported on the cylinder label after “EXP”.
Follow all regulations regarding the handling of pressurised cylinders.
Storage is supervised by local specialists at the hospital. Store the cylinders
in well-ventilated rooms or sheds where they are protected from rain and direct sunlight.
Protect the cylinders from impacts, falls, oxidizing and flammable materials, humidity, sources of heat or
ignition.
Storage in the pharmacy department
Keep the cylinders in a place exclusively reserved for the storage of medicinal gases, which is
well-ventilated, clean and kept locked. This place must include a special separate structure
for the storage of nitrous oxide cylinders.
Storage in the medical department
The cylinders must be stored in a place equipped with appropriate equipment to ensure that
they remain in an upright position.

6. Contents of the pack and other information

What NOXAP contains
NOXAP is a combination of gases.

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

Description of the appearance of NOXAP and contents of the pack
NOXAP is a compressed medicinal gas.
NOXAP is stored in high-pressure cylinders made of aluminium or aluminium and an outer
elastomeric layer. The valves closing the cylinders are made of stainless steel. The
cylinder packs are 2 l, 5 l, 10 l, 20 l, and 40 l.
NOXAP is introduced into these cylinders in gaseous form at a pressure of 200 bar. It is possible that
not all packs are marketed.
The colour code of the cylinder is light blue for the ogive and white for the body.

Marketing Authorisation Holder and Manufacturer
SOCIEDAD ESPANOLA DE CARBUROS METALICOS, S.A.
AVDA DE LA FAMA, 1
08940 CORNELLA DE LLOBREGAT
Sales concessionaire
Sapio Life S.r.l.
Via S. Pellico 48
20900 Monza
Italy

Tel. +39 039 83981

Manufacturer:
S.E. de Carburos Metálicos, S.A.
Polígon Nord-Est, C-35 km 59
08470 Sant Celoni (Barcelona)
Spain

This medicinal product is authorised in the Member States of the European Economic Area with the
following denominations:
Belgium: NOXAP 200 ppm mol/mol, medicinal gas, compressed
Netherlands: NOXAP 200 ppm mol/mol, medicinal gas, compressed
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, medicinal gas, compressed
Germany: NOXAP 200 ppm Mol/Mol Gas zur medizinischen Anwendung, compressed
Spain: NOXAP 200 ppm mol/mol, gas medicinal comprimido
Poland: NOXAP 200 ppm mol/mol, gaz medyczny, sprężony
Italy: NOXAP 200 ppm mol/mol, gas medicinale compresso

Complete with national data

NOXAP 800 ppm mol/mol, compressed medicinal gas

nitric oxide

Read this leaflet carefully before using this medicine as it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• If any side effects occur, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet:

• 1. What NOXAP is and what it is used for
• 2. What you need to know 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 is NOXAP and what is it used for

NOXAP is a gas mixture for inhalation use.
NOXAP is a compressed medicinal gas, consisting of a gas mixture containing 800 ppm
mol/mol of nitric oxide.

How is it used?
NOXAP must be administered exclusively by healthcare professionals and is reserved
exclusively for hospital use. NOXAP is indicated in the following conditions:

• 1. In newborns with oxygen deficiency in the blood(hypoxemic respiratory failure) due to various causes. NOXAP improves oxygenation and reduces the need for extracorporeal circulation.
• 2. In pediatric and adult patients undergoing cardiac surgery with acute pulmonary hypertension(pulmonary hypertension). NOXAPreduces pulmonary hypertension and the risk of right heart failure.

2. What you need to know before using NOXAP

Do not use NOXAP in the following cases:

• Newborns with documented tendency to right-to-left shunt or affected by significant left-to-right shunt.
• Patients with congenital or acquired deficiency of methemoglobin reductase (MetHb reductase) or glucose-6-phosphate dehydrogenase (G6PD).

Take special care with NOXAP:

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

Use of other medicines
Tell your doctor if you are taking or have recently taken any other medicines, including those
obtained without a prescription.

• Oxygen: in the presence of oxygen, nitric oxide rapidly oxidizes producing substances that are toxic to the lungs. To avoid this situation, treatment with NOXAP is accompanied by continuous monitoring.
• NO donors: some cardiological medicines, such as sodium nitroprusside and nitroglycerin, may have an additive effect to NOXAP, increasing the risk of methemoglobinemia.
• Drugs that increase methemoglobin concentrations: when alkyl nitrates, sulfonamides and prilocaine are administered together with nitric oxide, there is an increased risk of methemoglobinemia.
• With the administration of vasoconstrictors (almitrine, phenylephrine), prostacyclin and phosphodiesterase inhibitors, synergistic effects have been reported, but without an increase in adverse events.
• Inhaled nitric oxide has been used simultaneously with tolazoline, dopamine, dobutamine, norepinephrine, steroids and surfactants, without observing pharmacological interactions.

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

Pregnancy and breastfeeding
NOXAP should not be used during pregnancy unless the clinical conditions of the women
require treatment with NOXAP.
Adverse effects are predictable as methemoglobin is considered harmful to the fetus, and nitric oxide has shown a potential genotoxic effect given by the induction of structural alterations of DNA.
During treatment with NOXAP, breastfeeding should be discontinued.

Driving and operating machinery
No adverse events related to the ability to drive vehicles and operate machinery have been reported.

3. How to use NOXAP

NOXAP must be administered exclusively by healthcare professionals and is reserved
exclusively for hospital use.
NOXAP is administered by inhalation through a system that delivers the
prescribed nitric oxide concentration to the lungs, diluting NOXAP in a mixture of oxygen and air.
The doctor will determine the dosage and duration of treatment with NOXAP.

If you receive more NOXAP than you should, the delivery system will activate an alarm signal. At
that point, the doctor will reduce or stop the administration of NOXAP, then establish the
most appropriate treatment to follow.

If you stop receiving NOXAP
Towards the end of treatment, the doctor will gradually reduce the dosage of NOXAP.
Treatment with NOXAP should not be stopped abruptly, but gradually reduced
in order to allow the lungs to adapt to the normal oxygen concentration in the air.
If you have any doubts about the use of this medicine, consult your doctor or other healthcare professionals.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
The doctor will report and closely monitor any side effects. It is unlikely that you will be able to ascertain these side effects on your own.

Blood and lymphatic system disorders

• An elevated concentration of nitric oxide in the blood may determine a risk of methemoglobinemia. In this case, the blood's ability to transport oxygen may be reduced. If this occurs, the doctor will immediately reduce the dosage of nitric oxide to allow the blood to recover its normal oxygen-carrying capacity. In pediatric patients and other subjects with reduced levels of the methemoglobin reductase enzyme, this risk may increase. The formation of methemoglobin at serum levels > 5% with inhaled nitric oxide at concentrations < 20 ppm is very rare (may affect up to 1 in 10,000 people).
• Bleeding time: a preclinical study revealed that inhaled nitric oxide increases bleeding time. However, controlled clinical studies have not shown significant differences between the control group and the treatment group regarding hemorrhagic complications.

Systemic disorders and conditions related to the site of administration

• In 30-45% of cases, a lack of response to treatment may be observed.
• Significant increases in NO levels with low therapeutic doses (< 20 ppm) of inhaled NO, as well as evidence of clinical NO toxicity, are a very rare complication (may affect up to 1 in 10,000 people).
• Abrupt discontinuation of therapy with inhaled nitric oxide very often (very common frequency: may affect more than 1 in 10) causes rapid rebound reactions characterized by intense pulmonary vasoconstriction and hypoxemia.

If any side effect gets worse, or if you notice any side effects not listed in this leaflet,
please tell your doctor or other healthcare professionals.

Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. You can also report side effects directly through the national reporting system at
https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects you can help provide more information on the safety of
this medicine.

5. How to store NOXAP

Keep this medicine out of the sight and reach of children.
Do not use NOXAP after the expiry date which is reported on the cylinder label after “EXP”.
Follow all regulations regarding the handling of pressurised cylinders.
Storage is supervised by local specialists at the hospital. Store the cylinders
in well-ventilated rooms or sheds where they are protected from rain and direct sunlight.
Protect the cylinders from impacts, drops, oxidising and flammable materials, humidity, sources of heat or
ignition.
Storage in the pharmacy department
Keep the cylinders in a place exclusively reserved for the storage of medicinal gases, which is
well-ventilated, clean and locked. This place must include a special separate structure
for the storage of nitric oxide cylinders.
Storage in the medical department
The cylinders must be stored in a place equipped with appropriate equipment to ensure that
they remain in an upright position.

6. Contents of the pack and other information

What NOXAP contains
NOXAP is a combination of gases.

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

Description of the appearance of NOXAP and contents of the pack
NOXAP is a compressed medicinal gas.
NOXAP is stored in high-pressure cylinders made of aluminium or aluminium and an outer
elastomeric layer. The valves closing the cylinders are made of stainless steel. The cylinder packs are 2 l, 5 l, 10 l, 20 l, and 40 l.
NOXAP is introduced into these cylinders in gaseous form at a pressure of 200 bar. It is possible that
not all packs are marketed.
The cylinder colour code is light blue for the ogive and white for the body.

Marketing Authorisation Holder and Manufacturer
SOCIEDAD ESPANOLA DE CARBUROS METALICOS, S.A.
AVDA DE LA FAMA, 1
08940 CORNELLA DE LLOBREGAT
Sales concessionaire
Sapio Life S.r.l.
Via S. Pellico 48
20900 Monza
Italy

Tel. +39 039 83981

Manufacturer:
S.E. de Carburos Metálicos, S.A.
Polígon Nord-Est, C-35 km 59
08470 Sant Celoni (Barcelona)
Spain

This medicinal product is authorised in the Member States of the European Economic Area under the
following denominations:
Belgium: NOXAP 800 ppm mol/mol, medicinal gas, compressed
Netherlands: NOXAP 800 ppm mol/mol, medicinal gas, compressed
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, medicinal gas, compressed
Germany: NOXAP 800 ppm Mol/Mol Gas zur medizinischen Anwendung, compressed
Spain: NOXAP 800 ppm mol/mol, gas medicinal comprimido
Poland: NOXAP 800 ppm mol/mol, gaz medyczny, sprężony
Italy: NOXAP 800 ppm mol/mol, gas medicinale compresso

To be completed with national data