NITROUS OXIDE FOR MEDICAL USE LIQUID LINDE, 98%, MEDICAL CRYOGENIC GAS IN A FIXED CRYOGENIC CONTAINER

Introduction

PACKAGE LEAFLET: INFORMATION FOR THE USER

NITROUS OXIDE MEDICINAL LINDE,

98.0%, cryogenic medicinal gas in fixed cryogenic container

Nitrous Oxide

Read all of this leaflet carefully before you start using this medicine.

• Keep this 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 leaflet. See section 4.

Contents of the package leaflet

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

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

Nitrous Oxide is an inhalation gas that belongs to the group of general anesthetics

(Nervous system and central).

This medicinal product is for hospital use only.

Treatment with Nitrous Oxide is indicated in the following cases:

• As an adjunct to general anesthesia, in association with all anesthetic agents administered by intravenous or inhalation route.

As an adjunct to analgesia in the operating room or delivery room.

2. What you need to know before you start using Nitrous Oxide Medicinal Linde

Nitrous Oxide is a combustible, it allows and accelerates combustion.

Do not use Nitrous Oxide Medicinal 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), emphysema (bronchial obstruction), or have air in the pericardium (membrane surrounding the heart) due to injury or disease, e.g., due to tobacco, 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 been diagnosed with untreated folate or vitamin B12 deficiency, or have genetic alterations in the enzyme system related to vitamin metabolism, as the use of nitrous oxide could increase this deficiency.

Be careful with Nitrous Oxide Medicinal 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, as there is a high risk of dependence on nitrous oxide if you take it repeatedly.

Your doctor will decide when Nitrous Oxide Medicinal Liquid 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 Nitrous Oxide Medicinal Linde with other medicines

Nitrous Oxide Medicinal Liquid Linde potentiates the hypnotic effects of intravenous or inhalation 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

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.

Pregnancy

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

• Obstetric anesthesia:

Due to the rapid passage through the placental barrier, it is recommended to interrupt the administration of Nitrous Oxide Medicinal Liquid Linde if the time between the induction of anesthesia and the extraction of the fetus exceeds 20 minutes. Avoid using Nitrous Oxide Medicinal Liquid Linde in case of fetal distress.

• Obstetric analgesia:

The use of Nitrous Oxide Medicinal Liquid Linde 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 this medicine.

Driving and using machines

It is recommended not to drive vehicles or use machines for 24 hours after anesthesia with Nitrous Oxide.

3. How to use NITROUS OXIDE MEDICINAL LINDE

Your doctor will determine the correct dose of Nitrous Oxide 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 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 normally used at doses between 50 and 70% of the inhaled gas volume.

If you use more NITROUS OXIDE MEDICINAL LINDE than you should

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

4. Possible side effects

Like all medicines, Nitrous Oxide Medicinal Linde can cause side effects, although not everyone gets them.

Frequent adverse reactions (at least 1 in 100, but less than 1 in 10 patients):

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

Uncommon adverse reactions (at least 1 in 1000, but less than 1 in 100 patients):

• Feeling of pressure in the middle ear.
• Swelling, increase in intestinal air.

Rare adverse reactions (at least 1 in 10,000, but less than 1 in 1,000)

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

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

- Paraparesis

Adverse reactions of unknown frequency (cannot be estimated from available data):

• Effects on nervous function, sensations of numbness and weakness, generally in the legs.
• Disorders of the bone marrow and nervous functions, such as: megaloblastic anemia (increase in size of red blood cells), leukopenia (reduction in number of white blood cells), polyneuropathy (peripheral nervous system disorders), myelopathy (bone marrow disorders), headache
• Generalized convulsions.
• You may also experience psychiatric disorders, such as psychosis, confusion, anxiety, addiction.
• 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 leaflet, please tell your doctor.

5. Storage of NITROUS OXIDE MEDICINAL LINDE

• Keep this medicine out of the sight and reach of children.
• Fixed cryogenic containers must be installed in clean, well-ventilated areas without flammable materials.
• Storage of gases for medicinal use must be separate from gases for other uses.
• Fixed cryogenic containers must be protected from ignition sources, heat, combustible materials, and even static discharges.
• Fixed cryogenic containers must be protected from shock, impact, or fall hazards.
• No parking is allowed in the area where the fixed cryogenic containers are located.

Expiry date:

Do not use NITROUS OXIDE MEDICINAL LINDE after the expiry date:

6 months from the date of the last filling of the fixed cryogenic container.

6. Package contents and further information

Composition of NITROUS OXIDE MEDICINAL 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:

Fixed cryogenic containers are stainless steel cryogenic tanks of various capacities. The geometric capacity of each fixed cryogenic container is shown in liters and its corresponding volume in m3 of gas at 1 bar and 15°C:

Not all pack sizes are marketed

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.

Date of last revision of this 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

NITROUS OXIDE MEDICINAL LINDE is reserved for exclusive hospital use.

NITROUS OXIDE MEDICINAL LINDE must be used exclusively in a mixture with Medical 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 any incident, it is necessary to strictly follow the following instructions:

• Check the good condition of the material before use.
• Handle the material with clean, grease-free hands.
• Use protective glasses and clean gloves when handling the container.
• Do not touch cold or frosty parts.
• In case of cryogenic burn, rinse with plenty of water.
• If clothing becomes saturated with Nitrous Oxide, move away from the Nitrous Oxide source and areas that may pose a risk of inflammation, and remove the clothing.
• Open the valve of the fixed cryogenic containers progressively.
• Never exceed the maximum service pressure.
• Use specific fittings for Nitrous Oxide.
• Do not use intermediate fittings that allow connecting two devices that do not fit.
• Do not subject the flexible tube to a radius of curvature that is too small. Do not leave the flexible tube on the floor.
• Provide safety devices against overpressure in Nitrous Oxide circuits where there is a risk of liquid accumulation between two valves.
• In case of leakage, close the valve with a leak and check that the emergency device is activated.

IMPORTANT:

• Never introduce this liquid into a device that may contain combustible materials, and in particular, greasy substances.
• Never clean the containers that contain this liquid, the valves, the gaskets, the closing devices, as well as the circuits, with combustible products, and in particular, greasy substances.
• Do not apply greasy substances (vaseline, ointments, etc.) to the face of patients.
• Do not use aerosol generators (lacquers, deodorants, etc.), solvents (alcohol, gasoline, etc.) on the material, or in its vicinity.

Closing the valve of the container after use.

• Do not attempt to repair a faulty valve.
• Do not transfer liquid from one container to another.
• In case of leakage, close the valve that has a leak.
• Never use a container that has a leak.
• The average exposure limit (over 8 hours) to Nitrous Oxide is set at 25 ppm for occupational exposure.

Systematically ventilate the area of use, evacuating the exhaled gases to the outside and avoiding areas where they may accumulate. It is advisable, before any use, to ensure the possibility of evacuating gases in case of an accident or unexpected leak.