NITROUS OXIDE MEDICINAL GAS AIR LIQUIDE 98.0 V/V LIQUEFIED MEDICINAL GAS IN GAS CYLINDER

Introduction

Package Leaflet: Information for the User

MEDICINAL NITROUS OXIDE GAS

AIR LIQUIDE, 98.0% v/v, medicinal liquid gas in gas cylinder

Read the entire package leaflet carefully before starting to use this medication, as it contains important information for you

Keep this package leaflet, as you may need to read it again. If you have any questions, consult your doctor.

This medication has been prescribed to you only, and you should not give it to others, even if they have the same symptoms as you, as it may harm them.

If you experience side effects, consult your doctor, even if they are not listed in this package leaflet.

Contents of the package leaflet

1. What is Medicinal Nitrous Oxide and what is it used for
2. What you need to know before starting to use Medicinal Nitrous Oxide
3. How to use Medicinal Nitrous Oxide
4. Possible side effects
5. Storage of Medicinal Nitrous Oxide
6. Package contents and additional information

1. What is Medicinal Nitrous Oxide and what is it used for

Medicinal Nitrous Oxidebelongs to the group of general anesthetics (nervous system and central) and is an inhalation gas.

This medication is for hospital use only.

The use of this medication is indicated in the following cases:

• As an adjunct to general anesthesia, in combination with all anesthetic agents administered intravenously or by inhalation.
• As an adjunct to analgesia (pain relief) in the operating room or delivery room.

2. What you need to know before starting to use Medicinal Nitrous Oxide

Do not useMedicinal Nitrous Oxide:

• In patients who require ventilation with 100% oxygen.
• If you have pneumothorax (air in the lung space), air in the intracranial space, or if you suffer from bullous emphysema (obstruction of the bronchi), maxillofacial injuries, decompression sickness, after recent diving, after an air encephalogram, or in case of intestinal obstruction and after head injuries with loss of consciousness.
• In patients who have recently received a gas injection (such as SF6, C3F8, C2F6) as long as an intraocular gas bubble persists or during the 3 months following the last intraocular gas injection.
• Do not use for more than 24 hours or with a frequency of more than 4 days without medical supervision and hematological monitoring.
• If you have gas embolism, after recent diving, if you have been injected with air into the epidural space to determine the placement of the needle for epidural anesthesia, or during surgery in the middle ear, inner ear, and nasal sinuses.

Warnings and precautions:

Consult your doctor before starting to use Medicinal Nitrous Oxide.

• Nitrous oxide is a combustible gas that facilitates and accelerates combustion.
• As with all anesthetic gases, it is necessary to have an adequate ventilation system in the place of use of nitrous oxide.
• Nitrous oxide should not be administered with less than 21% oxygen.
• Nitrous oxide is heavier than air and can accumulate in low-lying areas, making the atmosphere hazardous.
• In patients with heart failure, if hypotension (low blood pressure) or heart failure occurs during the administration of nitrous oxide, stop the administration of the gas immediately.
• In patients who have undergone nasal and inner ear surgery.
• Prolonged and frequent use of nitrous oxide can cause serious blood disorders.
• It should not be used for more than a total of 24 hours or with a frequency of more than 4 days without specialized clinical supervision.
• Vitamin B12 levels should be evaluated in patients with risk factors such as alcoholic patients, patients with anemia or gastric problems, elderly patients, or patients with a poor or vegetarian diet.

Vitamin B12 levels should be evaluated in patients with risk factors for vitamin B12 deficiency before using anesthesia with nitrous oxide. Risk factors may include alcoholic patients, patients with anemia, atrophic gastritis, elderly patients, and those with a vegetarian diet or who have used medication that may interfere with vitamin B12 and/or folate metabolism. Vitamin B12 supplements should be given in case of repeated or prolonged administration.

In patients with undiagnosed subclinical vitamin B12 deficiency, neurological toxicity has occurred after a single exposure to nitrous oxide during general anesthesia.

Ear pain, and/or middle ear disorders, and/or eardrum rupture may occur in case of Eustachian tube obstruction due to increased pressure in the tympanic cavity.

Patients diagnosed with and/or at risk of intracranial hypertension should be monitored, as an increase in intracranial pressure has been observed during the administration of nitrous oxide in some patients with intracranial disorders.

Pediatric population

Rarely, nitrous oxide can cause respiratory depression in neonates. The newborn should be reviewed for possible respiratory depression when nitrous oxide is used during delivery.

Use ofMedicinal Nitrous Oxidewith other medications

Tell your doctor if you are using, have recently used, or may need to use any other medication.

Administration of nitrous oxide is contraindicated in patients with a persistent intraocular gas bubble after intraocular gas injection and/or patients who have received an intraocular gas injection in the previous 3 months, as it may cause significant vision disorders due to the expansion of the intraocular gas.

Nitrous oxide potentiates the hypnotic effects (drowsiness, sleep) of central nervous system depressant drugs (intravenous or inhaled anesthetics, tiopental, benzodiazepines, morphinics, halogenated, and psychotropics), so the dose of these should be reduced when administered at the same time.

Medications that interfere with vitamin B12 and/or folate metabolism may potentiate the inactivation of vitamin B12 by nitrous oxide.

Pregnancy and Breastfeeding

Nitrous oxide can be used during pregnancy if clinically necessary.

When nitrous oxide is used near birth, newborns should be monitored for possible adverse effects.

Nitrous oxide can be used during breastfeeding.

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor before using this medication.

Driving and using machines

It is recommended not to drive vehicles, not to use machines, and not to perform other psychomotor activities until you have recovered the same level of alertness as before the administration of nitrous oxide.

3. How to use Medicinal Nitrous Oxide

Medicinal Nitrous Oxide gas cylinders are intended exclusively for hospital use.

Nitrous oxide should only be administered in the operating room or delivery room, mixed with oxygen.

During pregnancy, it is recommended not to exceed a concentration of 50% nitrous oxide in the inhaled mixture.

Your doctor will determine the necessary dose of nitrous oxide, which will be administered through a system suitable for your needs, ensuring the supply of the correct amount of oxygen.

If you use moreMedicinal Nitrous Oxidethan you should

In case of overdose, there is a risk of cyanosis (bluish discoloration of the skin and mucous membranes due to lack of oxygen in the blood) and hypoxia (lack of oxygen in the blood). In these cases, the administration of nitrous oxide should be interrupted and air and oxygen should be administered to the patient.

In case of doubt, ask your doctor.

4. Possible side effects

Like all medications, Medicinal Nitrous Oxidecan cause side effects, although not everyone gets them.

The possibility of presenting a side effect is described by the following categories:

Frequent (> 1/100 to < 1/10):

Gastrointestinal disorders: Nausea, vomiting.

Uncommon (> 1/1,000 to < 1/100):

Nervous system disorders: paresthesia.

Psychiatric disorders: euphoria.

Unknown (cannot be estimated from available data):

Nervous system disorders: dizziness, myelopathy, neuropathy, increased intracranial pressure, generalized seizures.

Blood and lymphatic system disorders: megaloblastic anemia, pancytopenia (observed in prone circumstances (cobalamin deficiency, substance abuse)), leukopenia/agranulocytosis (observed after very high and prolonged exposures to tetanus treatment in the 1950s).

Eye disorders: severe visual impairment (caused by the expansion of an intraocular gas).

Ear and labyrinth disorders: ear pain, middle ear disorders, eardrum rupture (in case of Eustachian tube obstruction).

Respiratory, thoracic, and mediastinal disorders: respiratory depression (in the newborn, when nitrous oxide is used during delivery).

Metabolic and nutritional disorders: vitamin B12 deficiency.

Psychiatric disorders: disorientation.

Specific to analgesia:

Uncommon (≥1/1,000 to <1/100):

Nervous system disorders: excessive sedation.

Psychiatric disorders: agitation, anxiety, hallucinations, dreams.

Unknown (cannot be estimated from available data):

Nervous system disorders: headache.

Reporting of suspected adverse reactions.

Reporting suspected adverse reactions after authorization of the medication is important. It allows for continued monitoring of the benefit/risk balance of the medication. Healthcare professionals are asked to report any suspected adverse reactions through the national reporting system: Spanish Pharmacovigilance System for Human Use Medicines: www.notificaRAM.es

If you experience side effects, consult your doctor, even if they are not listed in this package leaflet.

5. Storage of Medicinal Nitrous Oxide

Keep this medication out of the reach and sight of children.

Do not use this medication after the expiration date stated on the packaging and label. The expiration date is the last day of the month indicated.

Regarding storage and transportation, the following should be taken into account:

Storage of gas cylinders in the storage area:

• Gas cylinders should be stored in a well-ventilated or ventilated area, protected from the weather and frost, clean, without flammable materials, reserved for the storage of medical gases, and locked.
• Empty and full gas cylinders should be stored separately.
• Gas cylinders should be protected from shock and fall hazards, heat sources or ignition, combustible materials, weather, and temperatures above 50°C.
• Upon delivery by the manufacturer, gas cylinders should be provided with an intact tamper-evident system.
• Empty gas cylinders should be kept in a vertical position, with the valve closed, to prevent any corrosion in the presence of moisture.

Storage of gas cylinders during use:

• Gas cylinders should be installed in a suitable location with appropriate material (with fixing belts) to keep them in a vertical position.
• Gas cylinders should be protected against shock and fall hazards, heat sources or ignition, and temperatures above 50°C.
• Pending use, gas cylinders should be kept with the valve closed, and excessive storage of containers should be avoided.

Transportation of gas cylinders:

• Gas cylinders should be transported in a vertical position and with suitable material (such as a cart provided with chains, barriers, or rings) to protect them from shock and fall hazards and to avoid the risk of burns in case of valve opening. Particular attention should be paid to the fixation of the manifold to avoid accidental rupture.

NOTE: Any theft or diversion of the product must be reported immediately to the authorities, the manufacturer, and the Spanish Agency for Medicines and Health Products.

6. Container Content and Additional Information

Composition of Medicinal Nitrous Oxide

• The active ingredient is nitrous oxide. Each dose contains 98% medicinal nitrous oxide.
• It does not contain other components (excipients).

Appearance of the Product and Container Content

Medicinal Nitrous Oxide is packaged in gas cylinders, available in the following sizes:

A B5 cylinder contains 3.75 kg and provides 2.03 m3 of gas at a pressure of 1 bar and 15º C

A B10 cylinder contains 7.5 kg and provides 4.05 m3 of gas at a pressure of 1 bar and 15º C

A B20 cylinder contains 15.0 kg and provides 8.10 m3 of gas at a pressure of 1 bar and 15º C

A B43 cylinder contains 32.25 kg and provides 17.42 m3 of gas at a pressure of 1 bar and 15º C

A B50 cylinder contains 37.5 kg and provides 20.25 m3 of gas at a pressure of 1 bar and 15º C

Marketing Authorization Holder:

AIR LIQUIDE Santé INTERNATIONAL

75 – Quai D`Orsay

75007 – Paris (FRANCE)

Manufacturer:

Air Liquide Santé FRANCE

23 Rue d’Athènes Z.I. du Bois Briand, Nantes Cedex 03, 44336,

France

Air Liquide Healthcare España, S.L.

Polígono Industrial A Uceira, Vial 7, parcela B12-13, 32500

O Carballiño, Ourense – Spain

Date of the Last Revision of this Prospectus: April 2023

“Detailed and updated information about this medication is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.es/”.

Instructions for Use and Handling Directed to the Healthcare Professional

Nitrous oxide is reserved for exclusive hospital use.

Medicinal Nitrous Oxide must be used exclusively mixed with Medicinal Oxygen; the oxygen concentration (FiO2) should never be less than 21%.

To avoid accidents, the following instructions will be respected:

• Liquid projection causes severe cryogenic burns (very cold). In case of burns, rinse abundantly with water.
• Take into account that the gas pressure in the cylinder remains constant (44 bar at 15 ºC), regardless of the residual liquid level, and is not a reflection of the remaining amount. When the cylinder no longer contains gas, and only at that moment, the pressure drops rapidly. Only the weight of the gas cylinder allows calculating its content during use.
• Ventilate, if possible, the place of use.
• Check the good condition of the materials before use.
• Perform any manipulation of nitrous oxide containers wearing clean gloves, adapted to this use, and protective glasses.
• Never touch the cold or frosty parts of the material.
• Do not manipulate a gas cylinder whose valve is not protected by a tulip.
• Handle the material with clean and grease-free hands.
• Handle gas cylinders wearing clean gloves and safety shoes.
• Hold the gas cylinders with a suitable means (chains, hooks, etc.) to keep them in a vertical position and avoid any fall.
• Never force the placement of a gas cylinder in a support where it fits with difficulty.
• Do not lift the gas cylinder by its valve.
• For gas cylinders: use a specific nitrous oxide connector.
• Use a manoreducer with a flowmeter that can withstand a pressure of at least 1.5 times the maximum service pressure of the gas cylinder.
• Use flexible connectors to the wall outlets provided with specific connections for Medicinal Nitrous Oxide.
• Do not use an intermediate connector that allows connecting two devices that do not fit.
• Open the valve progressively.
• Never force the valve to open it.
• Purge the gas cylinder outlet before connecting the manoreducer to eliminate possible dust particles.
• Never position yourself in front of the valve outlet, but always on the opposite side of the manoreducer, behind the gas cylinder and away from it. Never expose the patient to the gas flow.
• Verify previously the compatibility of the materials in contact with Medicinal Nitrous Oxide, in particular using connection gaskets to the manoreducer intended for this gas. Check the condition of the gaskets.
• Do not smoke, do not approach a flame, and do not grease.

Important:

• Never introduce this gas into a device that may be suspected of containing combustible bodies and, in particular, fatty bodies.
• Never clean with combustible products and, in particular, fatty bodies, the containers that contain this gas, the valves, gaskets, closing devices, as well as the circuits.
• Do not apply fatty substances (vaseline, ointments, etc.) to the face of patients.
• Do not use aerosol generators (hair spray, deodorants, etc.), solvents (alcohol, gasoline, etc.) on the material or in its proximity.
• Close the valve of the gas cylinder after use.
• Do not attempt to repair a faulty valve.
• Do not transfer gas from one cylinder to another.
• In case of leakage, close the valve that presents a leak.
• Ventilate the room where the containers are located.
• Never use a gas cylinder that presents a leak.
• In case of valve opening with a high flow and frost formation, do not use the gas cylinder and contact the manufacturer.
• When the ambient temperature is low, or in case of high consumption that causes the cooling of the gas cylinder, the flow may decrease, even interrupt, due to insufficient pressure in the gas cylinder.
• Avoid using the Medicinal Nitrous Oxide gas cylinders at a temperature below 0 ºC to avoid a pressure drop in case of intensive use.
• Keep empty gas cylinders with the valve closed to avoid any corrosion due to the presence of humidity.
• Never use Medicinal Nitrous Oxide for leak tests, for powering pneumatic tools, and for blowing pipes.
• The average exposure limit value (for 8 hours) to nitrous oxide is set at 50 ppm for personnel exposure.
• Perform systematic ventilation of the place of use, evacuating the exhaled gases to the outside and avoiding places where they could accumulate. It is convenient, before any use, to ensure the possibility of evacuating gases in case of an accident or unexpected leak.

“Detailed information about this medication is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.es”