NITROUS OXIDE MEDICAL LINDE, 98.0% MEDICINAL LIQUEFIED GAS

Introduction

Package Leaflet: Information for the User

MEDICINAL NITROUS OXIDE LINDE,

98.0% liquefied medicinal gas

Nitrous Oxide

Read this package leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this package leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• If you experience any side effects, talk to your doctor or pharmacist, even if they are not listed in this package leaflet. See section 4.

Contents of the package leaflet

1. What is MEDICINAL NITROUS OXIDE LINDE and what is it used for
2. What you need to know before you start using MEDICINAL NITROUS OXIDE LINDE
3. How to use MEDICINAL NITROUS OXIDE LINDE
4. Possible side effects
5. Storage of MEDICINAL NITROUS OXIDE LINDE
6. Package contents and further information

1. What is MEDICINAL NITROUS OXIDE LINDE and what is it used for

Nitrous oxide is an inhaled gas that belongs to the group of general anesthetics (nervous system and central).

This medicine is for hospital use only.

Treatment with nitrous oxide 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 in the operating room or delivery room.

2. What you need to know before you start using MEDICINAL NITROUS OXIDE LINDE

Nitrous oxide is a combustible gas that allows and accelerates combustion.

Do not use MEDICINAL NITROUS OXIDE LINDE:

Inhalation of nitrous oxide can cause gas bubbles and gases trapped in body cavities can expand due to increased diffusion of nitrous oxide. Therefore, do not use nitrous oxide:

• If you need ventilation with pure oxygen.
• In patients with intraocular gas injection (e.g., SF6 or C3F8).
• If you have pneumothorax (air in the pleural cavity) or emphysema (bronchial obstruction), or have air in the pericardium (membrane surrounding the heart) due to injury or disease, e.g., due to smoking, air, or gas bubbles in the body.

• Do not use it for more than 24 hours in a row.
• If you have recently been diving and may be at risk of decompression sickness.
• If you have recently undergone cardiopulmonary bypass.
• If you have abdominal gas distension
• If you have severe heart failure (e.g., after cardiac surgery), as nitrous oxide could increase cardiac dysfunction.
• If you have persistent signs of confusion, altered cognitive function, or other signs that may be related to increased intracranial pressure, as nitrous oxide could increase intracranial pressure.
• If you have decreased level of consciousness or ability to collaborate and follow instructions, as nitrous oxide could decrease protective reflexes.
• If you have a diagnosed folate or vitamin B12 deficiency, untreated, or have genetic alterations in the enzymatic system related to vitamin metabolism, as the use of nitrous oxide could increase this deficiency.

Be careful with MEDICINAL NITROUS OXIDE LINDE:

Also, inform your doctor if you have or present any of the following symptoms/signs:

• If you have intestinal obstruction or heart failure.
• If you suffer from vitamin B12 deficiency.

-Ear discomfort, such as ear inflammation, as nitrous oxide could increase middle ear pressure.

• If you have a history of drug abuse because there is a high risk of dependence on nitrous oxide if you take it repeatedly.

Your doctor will decide when MEDICINAL NITROUS OXIDE LINDE is possible in your case.

Prolonged or repeated use of nitrous oxide can increase the risk of vitamin B12 deficiency, which can cause damage to the bone marrow or nervous system. Your doctor may require blood tests before and after treatment to evaluate the consequences of a possible vitamin B12 deficiency.

Using MEDICINAL NITROUS OXIDE LINDE with other medicines

MEDICINAL NITROUS OXIDE LINDE enhances the hypnotic effects of intravenous or inhaled anesthetics (thiopental, benzodiazepines, morphine, halogenated), so the dosage of these should be reduced.

Tell your doctor or pharmacist if you are using or have recently used other medicines, including those purchased without a prescription.

If you are taking other medicines that affect the brain or brain function, such as benzodiazepines (tranquilizers) or morphine, you should inform your doctor. Nitrous oxide can increase the effects of these medicines. Nitrous oxide, taken together with other sedatives or medicines that affect the central nervous system, increases the risk of side effects.

You should also inform your doctor if you are taking medicines with methotrexate (e.g., for rheumatoid arthritis), as nitrous oxide increases the side effects of these medicines.

Pregnancy, breastfeeding, and fertility

Pregnancy

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

During pregnancy, it is recommended not to exceed a concentration of 50% of MEDICINAL NITROUS OXIDE LINDE in the inhaled mixture.

• Obstetric anesthesia:

Due to the rapid passage through the placental barrier, it is recommended to interrupt the administration of MEDICINAL NITROUS OXIDE LINDE if the time between the induction of anesthesia and the extraction of the fetus exceeds 20 minutes. Avoid using MEDICINAL NITROUS OXIDE LINDE in case of fetal distress.

• Obstetric analgesia:

The use of MEDICINAL NITROUS OXIDE LINDE for this indication can only be performed if a safety flowmeter is available to prevent the administration of nitrous oxide at a concentration greater than 50%.

Breastfeeding

Consult your doctor before using this medicine.

Driving and using machines

It is recommended not to drive vehicles and not to use machines during the 24 hours following anesthesia with MEDICINAL NITROUS OXIDE LINDE.

3. How to use MEDICINAL NITROUS OXIDE LINDE

Your doctor will determine the correct dose of MEDICINAL NITROUS OXIDE LINDE and it will be administered through a system suitable for your needs, ensuring the supply of the correct amount of oxygen.

During treatment with nitrous oxide, you and the administration of this medicine must be monitored to ensure that the nitrous oxide is administered safely. After completing the administration, you should be monitored by healthcare personnel until you have recovered.

Nitrous oxide is normally administered in a gas mixture containing at least 21% oxygen to avoid the risk of hypoxia (oxygen deficiency). Nitrous oxide is usually used at doses between 50 and 70% of the inhaled gas volume.

If you use more MEDICINAL NITROUS OXIDE LINDE than you should

There is a risk of cyanosis and hypoxia. The administration of MEDICINAL NITROUS OXIDE LINDE should be interrupted and the patient ventilated (air or oxygen).

4. Possible side effects

Like all medicines, MEDICINAL NITROUS OXIDE LINDE can cause side effects, although not everyone gets them.

Common side effects (at least 1 in 100, but less than 1 in 10 patients):

• Nausea and vomiting.
• Dizziness, mild headache, euphoria.
• Feeling of intoxication.

Uncommon side effects (at least 1 in 1000, but less than 1 in 100 patients):

• Feeling of pressure in the middle ear.
• Swelling, increased air in the intestines.

Rare side effects (at least 1 in 10,000, but less than 1 in 1,000)

• Effects on nerve function, feeling of numbness or decreased strength or weakness, usually in the legs.

Very rare side effects (at least 1 in 10,000 people suffer from them):

-Paraparesis

Side effects of unknown frequency (cannot be estimated from available data):

• Effects on nerve function, sensations of numbness and weakness, generally in the legs.
• Disorders of the bone marrow and nervous system functions, such as: megaloblastic anemia (increase in red blood cell size), leukopenia (reduction in white blood cell count), polyneuropathy (peripheral nervous system disorders), myelopathy (bone marrow disorders), headache
• Generalized seizures.
• Psychiatric disorders, such as psychosis, confusion, anxiety, addiction, can also occur.
• Respiratory depression

If you think any of the side effects you are experiencing are serious, or if you notice any side effects not listed in this package leaflet, please tell your doctor.

5. Storage of MEDICINAL NITROUS OXIDE LINDE

Keep out of the sight and reach of children.

All rules for handling pressure vessels must be followed. Regarding storage and transportation, the following must be taken into account:

Storage of cylinders:

• Cylinders must 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 with a key.
• Empty and full cylinders must be stored separately.
• Cylinders must be protected from shock and fall hazards, heat sources or ignition sources, flammable materials, and temperatures above 50°C.
• Upon delivery by the manufacturer, cylinders must be equipped with an intact tamper-evident system.
• Empty cylinders must be kept in a vertical position with the valve closed to avoid any corrosion in the presence of moisture.

Storage of cylinders during use:

• Cylinders must be installed in a suitable location with suitable material (with fixing straps, etc.) to keep them in a vertical position.
• Cylinders must be protected against shock and fall hazards, heat sources or ignition sources, and temperatures above 50°C.
• While waiting for use, cylinders must be kept with the valve closed and excessive storage of containers must be avoided.

Transportation of cylinders:

• Cylinders must be transported with the help of suitable material (such as a cart equipped with chains, barriers, or rings) to protect them from shock and fall hazards and to avoid burn risk in case of valve opening.
• Particular attention must be paid to the fixation of the pressure regulator to avoid accidental rupture risks.
• During transportation in vehicles, cylinders must be securely fastened, always in a vertical position. Permanent ventilation of the vehicle is mandatory, and smoking is strictly prohibited.

Expiry date:

Do not use MEDICINAL NITROUS OXIDE LINDE after the expiry date stated on the packaging. The expiry date is the last day of the month indicated.

6. Package contents and further information

Composition of MEDICINAL NITROUS OXIDE LINDE:

• The active substance is: Nitrous oxide (N2O) in a concentration greater than 98.0% (v/v).
• It does not contain excipients.

Appearance of the product and package contents:

This medicine is packaged in cylinders at 44 bar pressure at 15°C. Cylinders can be made of steel, compact steel, aluminum, or compact aluminum in the following volumes (not all pack sizes are marketed):

• A 5-liter cylinder contains 3.75 kg and provides 2.1 m3 of gas at a pressure of 1 bar and 15°C.
• A 10-liter cylinder contains 7.5 kg and provides 4.1 m3 of gas at a pressure of 1 bar and 15°C.
• A 13-liter cylinder contains 10 kg and provides 5.4 m3 of gas at a pressure of 1 bar and 15°C.
• A 20-liter cylinder contains 15 kg and provides 8.1 m3 of gas at a pressure of 1 bar and 15°C.
• A 50-liter cylinder contains 37.5 kg and provides 20.3 m3 of gas at a pressure of 1 bar and 15°C.
• A block of twelve 50-liter cylinders contains 450 kg and provides 243.6 m3 of gas at a pressure of 1 bar and 15°C.

Marketing authorization holder:

LINDE GAS ESPAÑA, S.A.U.

Camino de Liria, s/n,

46530 Puzol, Valencia, Spain

Phone: 93.476.74.00 and 902.426.462

Manufacturer:

LINDE GAS ESPAÑA, S.A.U.

P.I. Can Pí de Vilaroch. Avd. Antonio Gaudí, 151. Rubí-08191 Barcelona, Spain.

LINDE GAS ESPAÑA, S.A.U.

Pol. Ind. Bañuelos. Ctra. Alcalá-Daganzo, km 3.8. C/ Haití 1, 28806 Alcalá de Henares. (MADRID)- Spain.

Date of last revision of this package leaflet: January 2020.

Detailed and updated information on this medicine is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS)

http://www.aemps.es

This information is intended only for healthcare professionals

MEDICINAL NITROUS OXIDE LINDE liquefied medicinal gas is reserved for exclusive hospital use.

MEDICINAL NITROUS OXIDE LINDE must be used exclusively in a mixture with medicinal oxygen; the oxygen concentration (FiO2) should never be less than 21%.

Repeated exposure or administration of nitrous oxide can lead to addiction. Healthcare professionals should be cautious with occupational exposure to nitrous oxide.

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

To avoid accidents, the following instructions must be respected:

• Liquid projection causes severe cold burns. In case of burns, rinse abundantly with water.
• Consider that the gas pressure in the cylinder remains constant (44 bar at 15°C) regardless of the residual liquid level. When the cylinder no longer contains gas, and only at that moment, the pressure drops rapidly. Only the weight of the cylinder allows estimating its contents during use.
• Ventilate if possible the area of use.
• Check the good condition of the materials before use.
• Perform any handling of MEDICINAL NITROUS OXIDE LINDE cylinders wearing clean gloves adapted to this use and protective glasses.
• Do not handle a cylinder whose valve is not protected by a tulip.
• Handle the material with clean and grease-free hands.
• Handle cylinders with a capacity of 50 liters or more wearing clean gloves and safety shoes.
• Secure the 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 cylinder in a support where it fits with difficulty.
• Never lift the cylinder by the valve.
• For cylinders, use a specific connector for nitrous oxide.
• Use a pressure regulator with a flowmeter that can withstand a pressure of at least 1.5 times the maximum service pressure of the cylinder.
• Use flexible connection elements to wall outlets equipped with specific nozzles for nitrous oxide.
• Never 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 outlet connector of the cylinder before connecting the pressure regulator to eliminate any possible dust particles.
• Never position yourself in front of the valve outlet, but always on the opposite side of the pressure regulator, behind the cylinder, and away from it. Never expose the patient to the gas flow.
• Check the compatibility of materials in contact with nitrous oxide, in particular, use connection gaskets to the pressure regulator intended for this gas. Check the condition of the gaskets.

IMPORTANT:

• Never introduce this gas into a device that may contain combustible materials, and in particular, greasy substances.
• Never clean the containers that contain this gas, the valves, the gaskets, the closing devices, as well as the circuits with combustible products, and in particular, greasy substances.
• Never apply greasy substances (vaseline, ointments, etc.) to the face of patients.
• Never use aerosol generators (lacquer, deodorants, etc.), solvents (alcohol, gasoline, etc.) on the material or in its proximity.
• Close the cylinder valve after use.
• Do not attempt to repair a faulty valve.
• Never transfer gas from one cylinder to another.
• In case of leakage, close the valve that presents a leak.
• Never use a cylinder that presents a leak.
• In case of valve opening with high flow and frost formation, do not use the bottle and contact the manufacturer.
• When the ambient temperature is low or in case of high consumption that causes cylinder cooling, the flow may decrease or even stop due to insufficient pressure in the cylinder.
• Avoid using MEDICINAL NITROUS OXIDE LINDE cylinders at a temperature below 0°C to avoid a pressure drop in case of intensive use.
• Keep empty cylinders with the valve closed to avoid any corrosion due to moisture.
• Never use MEDICINAL NITROUS OXIDE LINDE for leak tests, for powering pneumatic tools, and for blowing pipes.
• The average limit value for exposure (over 8 hours) to MEDICINAL NITROUS OXIDE LINDE is set at 25 ppm for personnel exposure.
• Perform systematic ventilation of the area of use, evacuating the exhaled gases to the outside and avoiding areas where they could accumulate. It is advisable, before any use, to ensure the possibility of evacuating gases in case of an accident or unexpected leak.