NITROUS OXIDE FOR MEDICAL USE, 98.0% V/V LIQUEFIED MEDICINAL GAS IN GAS CYLINDER

2. What you need to know before starting treatment with Medicinal Nitrous Oxide Carburos Metálicos

Do not useMedicinal Nitrous Oxide Carburos Metálicos

• If you need ventilation with pure oxygen.
• If you have undrained air embolisms, particularly intracranial or pneumothorax, or bullous emphysema.
• Do not use for more than 24 hours consecutively.

Warnings and Precautions

• If you have heart failure, monitor your blood pressure to avoid hypotension.
• If you are going to have ear surgery or surgery in adjacent air-filled spaces.

Use ofMedicinal Nitrous Oxidewith other medicines

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

Nitrous oxide potentiates the hypnotic effects of intravenous or inhaled anesthetics (thiopental, benzodiazepines, morphine, halogenated), so the dosage of these should be reduced.

You should also inform your doctor if you are taking medicines that contain methotrexate (e.g., for rheumatoid arthritis).

Pregnancy and breastfeeding and fertility

Pregnancy

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

Obstetric anesthesia:

Due to the rapid transfer across the fetoplacental barrier, it is recommended to interrupt the administration of nitrous oxide if the time between the induction of anesthesia and fetal extraction exceeds 20 minutes.

Avoid using nitrous oxide in case of fetal distress.

Obstetric analgesia:

The use of nitrous oxide for this indication can only be performed if a safety flowmeter is available that prevents the administration of nitrous oxide at a concentration greater than 50%.

Breastfeeding

Consult your doctor before using the medicine.

Driving and using machines

It is recommended not to drive vehicles and not to use machines for 24 hours after anesthesia with nitrous oxide.

3. How to use Medicinal Nitrous Oxide Carburos Metálicos

The nitrous oxide gas cylinders are intended for exclusive hospital use.

Nitrous oxide should only be administered in the operating room or delivery room.

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

If you use more Medicinal Nitrous Oxide Carburos Metálicos than you should:

In case of overdose, there is a risk of cyanosis and hypoxia. The administration of Medicinal Nitrous Oxide should be interrupted and the patient ventilated (air and oxygen).

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

The assessment of side effects is based on the following frequencies:

Very common: may affect more than 1 in 10 people

Common: may affect up to 1 in 10 people

Uncommon: may affect up to 1 in 100 people

Rare: may affect up to 1 in 1,000 people

Very rare: may affect up to 1 in 10,000 people

Unknown: cannot be estimated from the available data

Very common

• Nausea and vomiting.
• Hypoxia, for several minutes after the end of nitrous oxide administration

Common

• Middle ear disorders
• Temporary increase in pressure and/or volume of the body's air cavities, normal or pathological.
• Ocular hypertension

Uncommon

• Hallucinations (Psychodysleptic effects may occur in the absence of combination with another anesthetic)

Rare

• Paraparesis

Very rare

• Severe hematological disorders (megaloblastic anemia, agranulocytopenia) have been reported for treatments lasting more than 24 hours.
• Arrhythmia, heart failure
• Epilepsy, increased intracranial pressure
• Psychotic disorder, confusion, anxiety, euphoric mood
• Pneumothorax
• Hypotension

Unknown

• Myelopathy, subacute combined degeneration of the spinal cord, polyneuropathy, generalized seizures
• Addiction

Reporting of side effects

If you experience any side effects, talk to your doctor or pharmacist, even if they are not listed in this leaflet. You can also report them directly through the Spanish Medicines and Healthcare Products Agency (AEMPS) website: www.notificaRAM.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Medicinal Nitrous Oxide Carburos Metálicos

Keep this medicine out of the sight and reach of children

Storage of gas cylinders in the warehouse:

• Full gas cylinders should always be kept in a vertical position, with the valves closed.
• Do not use Medicinal Nitrous OxideCarburos Metálicosafter the expiry date stated on the packaging, after CAD.
• Gas cylinders should be stored in a well-ventilated or ventilated area, protected from the weather, away from 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, flammable materials, weather, and temperatures above 50°C.
• When delivered 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 avoid 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 fixation 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.
• While waiting to be used, 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 appropriate material (e.g., cart with chains, barriers, or rings) to protect them from shock and fall hazards and to avoid the risk of cryogenic burns in case of valve opening.
• Particular attention should be paid to securing the manoreducer to avoid accidental rupture risks.

6. Package contents and additional information

Composition ofMedicinal Nitrous OxideCarburos Metálicos

The active ingredient is nitrous oxide. The concentration is greater than 98.0% v/v.

It does not contain other excipients.

Appearance of the product and package contents

Medicinal Nitrous OxideCarburos Metálicosis presented in the form of pressurized gas cylinders. The gas cylinders can be made of steel or aluminum and have the following volumes: 0.5 L, 1 L, 2 L, 3 L, 4 L, 5 L, 7 L, 10 L, 13 L, 15 L, 20 L, 25 L, 30 L, 40 L, 50 L in liters. Not all pack sizes are marketed.

Marketing authorization holder

S.E. de CARBUROS METÁLICOS, S.A.

Av. de la Fama, 1

08940 Cornellà de Llobregat, Barcelona

Spain

Manufacturer

S.E. de CARBUROS METÁLICOS S.A.

Ctra. De Toledo, 7

28300 Aranjuez

SPAIN

AIR PRODUCTS TEMPLEMARS

Zona Industrial de l’Epinoy

59175 Templemars

FRANCE

This leaflet was approved in: October 2023

Detailed information on this medicine is available on the website of the Spanish Agency for Medicines and Healthcare Products (AEMPS) http://www.aemps.gob.es

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This information is intended only for healthcare professionals:

Nitrous oxide is reserved for exclusive medical use.

Medicinal nitrous oxide must be used exclusively in a mixture with medicinal oxygen; the oxygen concentration (FiO2) should never be less than 21%.

To avoid accidents, the following guidelines should be respected:

• Always keep the gas cylinder in a vertical position to avoid the risk of liquid projection, which could cause severe cryogenic burns. In case of burns, rinse abundantly with water.
• Consider that the gas pressure in the cylinder remains constant (50 bar at 15°C), 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 its contents to be estimated during use.
• Ventilate the area if possible.
• Check the condition of the materials before use.
• Perform any manipulation of nitrous oxide containers wearing clean, grease-free gloves and safety 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, grease-free hands.
• Handle gas cylinders wearing safety shoes when required.
• Secure the gas cylinders with a suitable means (chains, hooks, etc.) to keep them in a vertical position and avoid any falls.
• Never force the placement of a gas cylinder in a support where it fits with difficulty.
• Never lift the gas cylinder by its valve.
• Use a specific nitrous oxide connector.
• Use a manoreducer with a flowmeter that can withstand a pressure at least 1.5 times the maximum service pressure of the gas cylinder.
• Use connection hoses 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. Never open it fully.
• Purge the outlet of the gas cylinder before connecting the manoreducer to eliminate any 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.
• Check the compatibility of materials in contact with medicinal nitrous oxide, in particular, use 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 contain combustible bodies, particularly greasy bodies.
• Never clean the containers that hold this gas, the valves, gaskets, closing devices, and circuits with combustible products, particularly greasy bodies.
• Do not apply greasy substances (vaseline, ointments, etc.) to the patients' faces.
• 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 a leak, close the valve that has a leak.
• Ventilate the area where the containers are located.
• Never use a gas cylinder that has 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 or even stop due to insufficient pressure in the gas cylinder.
• Avoid using nitrous oxide gas cylinders at a temperature below 0°C to avoid a pressure drop in case of intensive use.
• Keep empty gas cylinders with the valve closed to avoid any corrosion in the presence of moisture.
• Never use medicinal nitrous oxide for leak tests, for powering pneumatic tools, and for blowing pipes.
• The average limit value for exposure (over 8 hours) to nitrous oxide is set at 25 ppm for exposure of personnel.
• Perform systematic ventilation of the area of use, evacuating the exhaled gases to the outside and avoiding areas 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.