Prospect: information for the user

MEDICAL NITROUS OXIDE GAS

AIR LIQUIDE, 98.0% v/v, medicinal gas in a gas cartridge

Read this prospect carefully before starting to use this medicine, as it contains important information for you

.Keep this prospect, as you may need to read it again.
.If you have any doubts, consult your doctor.

.This medicine has been prescribed only to you, and you must not give it to other people even if they have the same symptoms as you, as it may harm them.

.If you experience any adverse effects, consult your doctor, even if they are not listed in this prospect.

1. What is Medical Nitrous Oxide and how it is used

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

3. How to use Medical Nitrous Oxide

4. Possible adverse effects

5. Storage of Medical Nitrous Oxide

6. Contents of the package and additional information

Medical Nitrous Oxidebelongs to the group of general anesthetics (nervous and central systems) and is a gas for inhalation.

This medication is only for hospital use.

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

• Adjuvant to general anesthesia, in association with all anesthetic agents administered via intravenous or inhalation routes.

• Adjuvant to analgesia (pain relief) in the operating room or delivery room.

No useNitrous OxideMedicinal:

-In patients who require oxygen ventilation at 100%.

-If you have pneumothorax (air in the lung space), if you have air in the intracranial space or if you suffer from bullous emphysema (obstruction of the bronchi), if you have maxillofacial injuries, decompression sickness, after recent underwater immersion, after performing 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 there is a gas bubble in the intraocular space or during the 3 months following the last intraocular gas injection.

-Do not use for more than 24 hours or more than 4 days in a row, without medical supervision and hematological monitoring.

-If you have gas embolism, after recent underwater immersion, if air has been injected into the epidural space to determine the placement of the needle for epidural anesthesia, or during middle ear, inner ear, and nasal sinus surgery..

Warnings and Precautions:

Consult your doctor before starting to useNitrous OxideMedicinal.

-Nitrous oxide is a combustible gas, which 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.

-Do not administer nitrous oxide with less than 21% oxygen.

-Nitrous oxide is heavier than air, it can accumulate in low areas and make the atmosphere hazardous.

-In patients with heart failure, if hypotension (low blood pressure) or heart failure occurs during nitrous oxide administration, stop administering the gas immediately.

-In patients who have undergone nasal and inner ear surgery.

-Prolonged and frequent use of nitrous oxide can cause severe blood abnormalities.

-It should not be used for more than a total of 24 hours or more than 4 days in a row without specialized clinical supervision.

-Vitamin B12 levels should be evaluated in patients with risk factors such as alcoholics, patients with anemia or gastrointestinal problems, elderly patients, or patients with a poor diet or vegetarians.

Vitamin B12 levels should be evaluated in patients with risk factors for vitamin B12 deficiency before using nitrous oxide anesthesia. Risk factors may include alcoholics, patients with anemia, gastric atrophy, 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 tympanic membrane rupture may occur due to obstruction of the Eustachian tube due to increased pressure in the tympanic cavity.

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

Pediatric Population

Nitrous oxide may cause respiratory depression in neonates in rare cases. The newborn should be checked for possible respiratory depression when nitrous oxide is used during delivery.

Use ofNitrous Oxidewith other medications

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

Nitrous oxide is contraindicated in patients with a gas bubble in the intraocular space that persists after receiving an intraocular gas injection and/or patients who have received a recent intraocular gas injection within the past 3 months, as it may cause significant visual disturbances due to intraocular gas expansion.

Nitrous oxide potentiates the hypnotic effects (drowsiness, sleep) of central nervous system depressants (intravenous or inhaled anesthetics, thiopental, benzodiazepines, morphines, halogenated and psychotropic drugs), so the dose of these should be reduced when administered simultaneously.

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

Pregnancy and Lactation

Nitrous oxide may be used during pregnancy if clinically necessary.

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

Nitrous oxide may be used during lactation.

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

Driving and operating machinery

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

Medicinal Nitrous Oxide cartridges are intended forexclusively 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.

The doctor will determine the necessary dose of nitrous oxide, which will be administered through an appropriate system that ensures the supply of the correct amount of oxygen.

If you use moreMEDICINAL NITROUS OXIDE than you should

In case of overdose, there is a risk of cyanosis (blue 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, discontinue nitrous oxide administration and administer air and oxygen to the patient.

In case of doubt, ask your doctor.

Like all medications,Nitrous OxideMedicinalcan cause adverse effects, although not everyone will experience them.

The possibility of presenting an adverse effect is described using the following categories:

Frequent (> 1/100 to <1

Gastrointestinal disorders: Nausea, vomiting.

Rare (> 1/1,000 to <1

Nervous system disorders: paresthesia

Mental and behavioral disorders: euphoria.

Unknown (cannot be estimated from available data):

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

Blood and lymphatic system disorders: megaloblastic anemia, pancytopenia (observed in predisposed circumstances (cobalamin deficiency, substance abuse)), leukopenia/agranulocytosis (observed after very high and prolonged exposure 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.

Mental and behavioral disorders: Disorientation.

Specific to analgesia:

Rare (≥1 / 1,000 to <1

Nervous system disorders: Excessive sedation.

Mental and behavioral disorders: Agitation, anxiety, hallucinations, dreams.

Unknown (cannot be estimated from available data):

Nervous system disorders: Headache

Reporting of suspected adverse reactions.

The reporting of suspected adverse reactions after the 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 System of Pharmacovigilance of Medicinal Products for Human Use:www.notificaRAM.es

If you experience adverse effects, consult your doctor, even if they are not listed in this prospectus.

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

Do not use this medication after the expiration date that appears on the packaging 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 room:

-Gas cylinders must be stored in a well-ventilated or air-conditioned area, protected from the elements and frost, clean, free from flammable materials, reserved for the storage of medical gases andlocked with a key.

-Empty and full gas cylinders must be stored separately.

-Gas cylinders must be protected from shock and falling risks, heat sources or ignition, flammable materials, weather conditions, and temperatures above 50 °C.

-Upon delivery by the manufacturer, gas cylinders must be provided with an intact integrity guarantee system.

-Empty gas cylinders must be kept in an upright position, with the valve closed, to prevent any corrosion in the presence of humidity.

Storage of gas cylinders during use:

-Gas cylinders must be installed in a conditioned area with suitable material (with fixation belts) to maintain them in an upright position.

-Gas cylinders must be protected against shock or falling risks, heat sources or ignition, and temperatures above 50 °C.

-Before use, gas cylinders must be kept with the valve closed, and excessive storage of containers must be avoided.

Transportation of gas cylinders:

-Gas cylinders must be transported in an upright position and with suitable material (type of car provided with chains, barriers, or rings) to protect them from shock and falling risks and to prevent, thus, a risk of burns in case of valve opening. Special attention must also be paid to the fixation of the regulator to avoid accidental rupture.

NOTE: Any theft or diversion of the product must be immediately notified to the authorities, the manufacturer, and the Spanish Agency for Medicines and Medical Devices.

Composition of Medical Nitrous Oxide

-The active principle is nitrous oxide. Each dose contains 98% of Medical Nitrous Oxide.

-It does not contain other components (excipients).

Appearance of the product and contents of the package

Nitrous Oxide Medical is packaged in gas capsules, available in the following sizes:

A B5 capsule contains 3.75 kg and provides 2.03 m3of gas at a pressure of 1 bar and 15°C

A B10 capsule contains 7.5 kg and provides 4.05 m3of gas at a pressure of 1 bar and 15°C

A B20 capsule contains 15.0 kg and provides 8.10 m3of gas at a pressure of 1 bar and 15°C

A B43 capsule contains 32.25 kg and provides 17.42 m3of gas at a pressure of 1 bar and 15°C

A B50 capsule contains 37.5 kg and provides 20.25 m3of gas at a pressure of 1 bar and 15°C

Holder of the marketing authorization:

AIR LIQUIDE Santé INTERNATIONAL

75 – Quai D`Orsay

75007 – Paris (FRANCE)

Responsible for manufacturing:

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

Last review date of this leaflet: April 2023

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

Instructions for use and handling for healthcare professionals

Nitrous oxide is reserved for exclusive hospital use.

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

To avoid accidents, the following instructions will be respected:

•Cryogenic burns can occur when liquid is projected. In case of burn, abundantly rinse with water.

•Take into account that the gas pressure in the capsule remains constant (44 bar at 15°C), regardless of the residual liquid level, and is not a reflection of the remaining amount. When the capsule no longer contains gas, and only at that moment, the pressure drops rapidly. Only the weight of the gas capsule allows calculating its content during use.

•Ventilate, if possible, the area of use.

•Check the good condition of the materials before use.

•Perform any manipulation on nitrous oxide containers wearing clean, adapted gloves, and protective glasses.

•Never touch the cold or frosty parts of the material.

•Do not manipulate a gas capsule whose valve is not protected by a tulip.

•Manipulate the material with clean, grease-free hands.

•Manipulate gas capsules wearing clean gloves and safety shoes.

•Hold gas capsules with an appropriate means (chains, hooks, etc.) to keep them in a vertical position and prevent any fall.

•Never force the placement of a gas capsule in a support where it enters with difficulty.

•Do not lift the gas capsule by its valve.

•For gas capsules: use a specific nitrous oxide regulator.

•Use a flow regulator with a flowmeter that can admit a pressure, at least, equal to 1.5 times the maximum service pressure of the gas capsule.

•Use flexible connectors to the wall outlets provided with specific connections for Medical Nitrous Oxide.

•Do not use an intermediate regulator that allows connecting two devices that do not fit.

•Open the valve gradually.

•Never force the valve to open.

•Purge the outlet regulator of the gas capsule before connecting the flow regulator to eliminate any possible dust particles.

•Never stand in front of the valve outlet, but always on the opposite side of the flow regulator, behind the gas capsule, and away from it. Never expose the patient to the gas flow.

•Verify beforehand the compatibility of the materials in contact with Medical Nitrous Oxide, particularly using connection joints on the flow regulator designed for this gas. Check the condition of the joints.

•Do not smoke, do not approach a flame, and do not grease.

Important:

•Never introduce this gas into an apparatus 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, valves, joints, closure devices, and circuits.

•Do not apply greasy substances (vaseline, ointments, etc.) to the patients' faces.

•Do not use aerosol generators (lacquer, deodorants, etc.), solvents (alcohol, gasoline, etc.) on the material or in its vicinity.

•Close the valve of the gas capsule after use.

•Do not attempt to repair a defective valve.

•Do not transfer gas from one capsule to another.

•In case of leakage, close the valve with a defect in tightness.

•Ventilate the area where the containers are located.

•Do not use a gas capsule with a defect in tightness.

•In case of opening the valve with a high flow rate and formation of frost, do not use the gas capsule and contact the manufacturer.

•When the ambient temperature is low, or in case of high consumption that causes the cooling of the gas capsule, the flow rate may decrease, even interrupt, due to insufficient pressure in the gas capsule.

•Avoid using the Medical Nitrous Oxide gas capsules at a temperature below 0°C to prevent a pressure drop in case of intense use.

•Store empty gas capsules with the valve closed to prevent any corrosion due to the presence of humidity.

•Do not use Medical Nitrous Oxide for leak tests, for the feeding of pneumatic tools, and for blowing tubes.

•The average exposure limit (for 8 hours) to nitrous oxide is set at 50 ppm for the exposure of personnel.

•Perform systematic ventilation of the area of use, evacuating the expired gases to the outside and avoiding areas where they could accumulate. It is advisable, before any use, to ensure the possibility of evacuating the gases in case of an accident or unexpected leakage.

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