MEDICAL LIQUID OXYGEN LINDE CRYOGENIC MEDICAL GAS 99.5% V/V IN MOBILE CRYOGENIC CONTAINERS

Introduction

Package Leaflet: Information for the User

MEDICINAL LIQUID OXYGEN LINDE,

cryogenic medicinal gas, 99.5% v/v, in mobile cryogenic containers

Medicinal Oxygen

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

• Keep this leaflet, you may need to read it again. If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

1. What MEDICINAL LIQUID OXYGEN LINDE is and what it is used for
2. What you need to know before you use MEDICINAL LIQUID OXYGEN LINDE
3. How to use MEDICINAL LIQUID OXYGEN LINDE
4. Possible side effects
5. Storage of MEDICINAL LIQUID OXYGEN LINDE
6. Contents of the pack and other information

1. What MEDICINAL LIQUID OXYGEN LINDE is and what it is used for

MEDICINAL LIQUID OXYGEN LINDEis an inhalation gas that belongs to a group of medicines called medicinal gases. It is packaged in cryogenic containers that contain only pure oxygen.

Oxygen is an essential element for the body and is administered to increase its levels in the blood and, as a consequence, achieve greater transport of oxygen to all body tissues.

Treatment with oxygen is indicated in the following cases:

• Correction of oxygen deficiency of different origins that require the administration of oxygen at normal or high pressure.
• Feeding of respirators in anesthesia - resuscitation.
• Administration of inhalation medications via nebulizer.

2. Before using MEDICINAL LIQUID OXYGEN LINDE

Do not use MEDICINAL LIQUID OXYGEN LINDE:

This medicine cannot be used at high pressure in cases of untreated lung collapses (untreated pneumothorax). A lung collapse is a accumulation of gas in the thoracic cavity between the two lung membranes. If you have suffered a lung collapse previously, inform your doctor.

Be careful with MEDICINAL LIQUID OXYGEN LINDE:

• If you have a chronic lung disease such as bronchitis, emphysema, or asthma, and in severe cases of oxygen deficiency. You should inform your doctor about this.
• No fatty substances (vaseline, ointments, etc.) should be applied to the face of patients due to the risk of inflammation (see Section 6).
• Because it can be toxic to the lung or nervous system depending on the concentration and duration of application (see Section 3 and Section 6).

Precautions for use

• Oxygen should not be used in the presence of flammable materials: oils, lubricants, tissues, wood, paper, plastic materials, ... (see Section 6).
• If oxygen is applied at high pressure (hyperbaric oxygen therapy), there may be injuries caused by the high pressure in body cavities that contain air and are in communication with the outside. To avoid risks, compression and decompression should be slow (see Section 4).
• When using hyperbaric oxygen therapy, you should inform your doctor in case of:
• chronic obstructive pulmonary disease (COPD)
• or a pulmonary disorder caused by the loss of elasticity of lung tissue accompanied by severe respiratory difficulty (severe emphysema)
• or upper respiratory tract infections
• or recent middle ear surgery
• or thoracic surgery, at any time in the patient's life
• or uncontrolled high fever
• or severe epilepsy
• or fear of enclosed spaces (claustrophobia)
• or if you have had a lung collapse previously (an accumulation of air or gas in the thoracic cavity between the two lung membranes (pneumothorax))

• The oxygen conditioned in cryogenic containers is a liquid at cryogenic temperature (approx. -183°C), so it can cause severe frostbite when in contact with the skin.
• In case of frostbite, spray with water at room temperature for 15 minutes. Apply a sterile dressing. Seek medical attention.
• In case of eye contact, rinse eyes immediately with water at room temperature for at least 15 minutes. Seek medical attention.

Use in children

In newborns, especially if they are premature, there may be eye damage (retrolental fibroplasia) with certain concentrations of oxygen (see Section 4).

Use of other medicines and other forms of interaction

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

• The toxicity of oxygen can be increased if used at the same time as other medicines that also have an effect on the lungs: corticosteroids, some cancer medicines (bleomycin), sympathomimetics. This can also occur in the treatment of paraquat poisoning, when using X-rays, or in cases of hyperthyroidism or deficiency of vitamins C and E or glutathione.
• There are reports of interaction with amiodarone. The recurrence of bleomycin or actinomycin-induced lung damage can be fatal.
• Oxygen can also exacerbate respiratory depressions induced by alcohol.
• Among the medicines known to produce adverse effects are: adriamycin, menadione, promazine, chlorpromazine, thioridazine, and chloroquine. The effects will be particularly pronounced in tissues with high levels of oxygen, especially the lungs.

Pregnancy and breastfeeding

Consult your doctor or pharmacist before using any medicine.

During pregnancy, the use of oxygen at normal pressure (normobaric oxygen therapy) is allowed at low concentrations.

During rescue treatments, oxygen can also be used during pregnancy at high concentrations and high pressures.

There are no contraindications for using oxygen during breastfeeding periods.

Consult your doctor or pharmacist if you need advice before taking any medicine.

Driving and using machines

There is no data on the effect of medicinal oxygen on driving and using machines, so it is possible to drive but with extreme caution.

3. How to use MEDICINAL LIQUID OXYGEN LINDE

Follow exactly the administration instructions of oxygen indicated by your doctor.

MEDICINAL LIQUID OXYGEN LINDE is used by inhalation. The doctor will determine the correct dose of medicinal oxygen and administer it through a system suitable for your needs that guarantees the supply of the correct amount of oxygen.

Dosage.The usual dose is:

• In patients who breathe spontaneously (spontaneous ventilation) and have acute respiratory failure, oxygen is administered at a flow rate of 0.5 to 15 liters/minute. This may vary depending on the results of the analyses performed (gasometry).
• In patients who breathe spontaneously (spontaneous ventilation) and have chronic respiratory failure, oxygen is administered at a flow rate of 0.5 to 2 liters/minute. This may vary depending on the results of the analyses performed (gasometry).
• In patients who need help breathing (assisted ventilation), oxygen should be administered at a dose that allows achieving a minimum oxygen concentration of 21%, which can reach up to 100%.

Method of administration

• In patients without ventilation problems: oxygen can be administered by spontaneous ventilation with the help of nasal glasses, a nasopharyngeal tube, or a mask, which should be adapted to the oxygen flow.
• In patients with ventilation problems or who are anesthetized, oxygen is administered through special devices such as an endotracheal tube, laryngeal mask, through a tracheotomy that allows connection to assisted ventilation, or others.
• The administration of oxygen at high pressure (hyperbaric oxygen therapy) is performed in a hyperbaric chamber at a pressure of 2 to 3 atmospheres, and the duration of the sessions is between 90 minutes and 2 hours. These sessions can be repeated between 2 and 4 times a day depending on the indications and the patient's clinical condition.

Duration of treatment

As a general rule, high concentrations of oxygen should be used for the shortest possible time that allows achieving the desired result. The oxygen concentration administered should be reduced as soon as possible to the minimum concentration necessary.

• Oxygen concentrations up to 100% should not be given for more than 6 hours.
• Oxygen concentrations between 60-70% should not be given for more than 24 hours.
• Oxygen concentrations between 40-50% should not be given for more than 24 hours.
• Any oxygen concentration above 40% is potentially toxic after 2 days.

If you think the effect of MEDICINAL LIQUID OXYGEN LINDE is too strong or too weak, tell your doctor.

Read carefully the instructions for use (see Section 6).

If you use more MEDICINAL LIQUID OXYGEN LINDE than you should:

In some situations, too much oxygen can affect breathing and exceptionally produce anesthesia or unconsciousness due to carbon dioxide.

The toxic effects of oxygen vary depending on the pressure of the inhaled oxygen and the duration of exposure.

At low pressure (from 0.5 to 2.0 bars), these effects are more likely in the pulmonary region than in the central nervous system (brain and spinal cord). At high pressure (hyperbaric oxygen therapy), the opposite occurs.

The effects in the pulmonary region include shortness of breath (hypoventilation), cough, and chest pain. The effects in the central nervous system include nausea, dizziness, anxiety, and confusion, up to spasms, loss of consciousness, and epileptic seizures.

If any of these symptoms appear, you should contact your doctor or hospital or call the Toxicology Information Service, phone: 91 562 04 20.

In case of excessive oxygen use, the inhaled oxygen concentration should be decreased, and symptomatic treatment is recommended.

4. Possible side effects

Like all medicines, MEDICINAL LIQUID OXYGEN LINDE can cause side effects, although not everybody gets them.

When oxygen is administered through nasal glasses, it can cause dryness of the nasal and labial mucosa.

Side effects usually appear when high concentrations of oxygen (above 70%) are used and after prolonged treatment (at least 6-12 hours).

The following side effects are uncommon (affect 1 to 10 users in 1,000):

• Respiratory, thoracic, and mediastinal disorders: atelectasis (lung collapse), dry cough, and pain associated with breathing.
• With high-pressure oxygen (hyperbaric oxygen therapy): ear and labyrinth disorders, such as a feeling of pressure in the middle ear and rupture of the eardrum.

The following side effects are rare (affect 1 to 10 users in 10,000):

• Eye disorders: eye damage that can affect vision (retrolental fibroplasia) in premature newborns exposed to high concentrations of oxygen.

The following side effects are very rare (affect less than 1 user in 10,000):

• Respiratory, thoracic, and mediastinal disorders: severe difficulty breathing due to acute lung failure (acute respiratory distress syndrome).
• With high-pressure oxygen (hyperbaric oxygen therapy): nervous system disorders, such as anxiety, confusion, loss of consciousness, and epileptic seizures.

Other side effects of unknown frequency are:

• Apnea (interruption of breathing): in patients with chronic respiratory failure.
• Lesions in the nasal sinuses, pneumothorax (presence of air in the thoracic cavity), nausea, dizziness, temporary loss of vision, pain, and muscle contraction with high-pressure oxygen (hyperbaric oxygen therapy).
• Claustrophobia crisis: in patients undergoing high-pressure oxygen therapy in hyperbaric chambers.
• Anemia.
• Affecting various organs with high concentrations of oxygen in long-term treatments: heart (it can also decrease heart rate when 100% oxygen is administered in short periods), liver, kidneys, and lungs (pulmonary fibrosis).
• Pulmonary malformations (bronchopulmonary dysplasia), hemorrhages in different locations (subependymal and intraventricular) and intestinal damage with tissue destruction (necrotizing enterocolitis) in newborns and premature babies.

If you think any of the side effects you are suffering from is serious, or if you notice any side effect not mentioned in this leaflet, tell your doctor.

5. Storage of MEDICINAL LIQUID OXYGEN LINDE

Keep MEDICINAL LIQUID OXYGEN LINDE out of the reach and sight of children.

Storage of containers

o Containers must be stored in a well-ventilated area, protected from the weather, clean, without flammable materials, reserved for the storage of medical gases, and can be locked.

o Empty and full containers must be stored separately.

o Keep containers always in a vertical position.

o Containers must be protected from the risk of blows or falls.

o Store at temperatures between -20°C and +50°C.

o Ensure that highly flammable or combustible products are not stored in the same area.

o Ensure that containers are stored away from heat sources or ignition sources.

o Do not smoke near the container.

Storage of containers in the user's service and at home:

o The container must be installed in a location that allows protecting it from the risks of blows and falls, heat sources or ignition sources, temperatures equal to or above 50°C, flammable materials, and weather conditions.

o Keep containers always in a vertical position.

o Excessive storage should be avoided.

Transport of containers:

o Do not park vehicles in the oxygen transfer area.

o The transport of containers must be carried out according to international regulations for the transport of hazardous goods.

o Containers must be transported with the help of suitable material (such as a cart equipped with chains, barriers, or rings) to protect them from the risk of blows or falls.

o During transport in vehicles, containers must be well secured, preferably in a vertical position. Permanent ventilation of the vehicle is mandatory, and smoking is strictly prohibited.

Expiration date

Do not use MEDICINAL LIQUID OXYGEN LINDEafter the expiration date indicated on the package label.

6. ADDITIONAL INFORMATION

Composition of OXÍGENO MEDICINAL LÍQUIDO LINDE

• The active ingredient is Oxygen.
• Without excipients.

Presentation of OXÍGENO MEDICINAL LÍQUIDO LINDE and container content

OXÍGENO MEDICINAL LÍQUIDO LINDE is a cryogenic medicinal gas. Oxygen is a colorless, odorless, and tasteless gas. When liquefied, it has a slightly blue color.

It is stored in mobile cryogenic tanks made of stainless steel.

The mobile cryogenic containers are made with a double layer of stainless steel.

These are supplied under pressure in the form of a liquid at very low temperature (approximately -183°C) in tanks with thermal insulation designed specifically for storing cryogenic liquids. Do not approach a flame. Do not grease. Instructions for use / handling Do not smoke. The capacity of the tanks is 30 and 45 liters

Marketing authorization holder

Linde Médica, S.L.U.

Camino de Liria, s/n, apartado de correos nº 25,

46530 Puzol, Valencia

Spain

Manufacturer

Abelló Linde, S.A. Polígono Industrial Can Pí de Vilaroch, Avda. Antonio Gaudí, 151, Rubí, 08191 Barcelona

S.E. DE CARBUROS METALICOS, S.A. Barrio Chaco s/n (Arrigorriaga (Vizcaya)) - 48480 - Spain S.E. DE CARBUROS METALICOS, S.A. Crta. Sevilla a Granada, Km. 9,6. Pol. Ind. La Red (Alcalá de Guadaira (Sevilla)) - 41500 – Spain

S.E. DE CARBUROS METALICOS, S.A. Pol. Ind. Can Rubiol. Celleters, 142 (Marratxí (Islas Baleares)) - 07141 - Spain

S.E. DE CARBUROS METALICOS, S.A.

Avda. Madrid, 82.

Laguna de Duero (Valladolid)

Abelló Linde, S.A.

Camino de Lliria, s/n

Puçol (Valencia), 46530 – Valencia.

Abelló Linde, S.A.

Pol. Ind. El Bierzo, C/Hamburgo, 16.

Ponferrada, 24400 León.

Instructions for use / handling

Do not smoke

Do not approach a flame

Do not grease

In particular:

• Never introduce this gas into a device that is suspected to contain combustible materials, especially if they are of a greasy nature.
• Never clean with combustible products, especially if they are of a greasy nature, either the devices that contain this gas or the valves, gaskets, seals, and closing devices.
• Never apply any greasy substance (vaseline, ointments, etc.) to the face of patients.
• Do not use aerosols (hair spray, deodorant, etc.) or solvents (alcohol, perfume, etc.) on the material or near it.

The containers of OXÍGENO MEDICINAL are reserved exclusively for therapeutic use.

For the specific case of liquid oxygen, additional particularities of the product must also be considered, which must be taken into account as precautions for its use and handling:

• Oxygen is a gas heavier than air, which can accumulate in low points after the vaporization of the liquid and make the atmosphere dangerous.
• Oxygen at atmospheric pressure is a liquid at very low temperature (around -183°C) and can cause frostbite if it comes into contact with the skin due to splashes or handling of the liquid without adequate protective equipment.
• One liter of liquid oxygen releases 850 liters of gas by vaporization and heating to ambient temperature. The expansion of liquid oxygen by heating is 850 times its liquid volume, and therefore, precautions must be taken against overpressure in closed volumes (equipment and installations) and over-oxygenation of materials and the atmosphere of the premises.

To avoid any incidents, it is necessary to strictly respect the following guidelines:

1. Verify the good condition of the material before its use
2. Verify at the time of delivery by the manufacturer that the bottle is equipped with an intact tamper-evident system
3. Handle the material with clean and grease-free hands
4. Use protective glasses and clean gloves intended for this use.
5. Do not touch the cold or frosty parts.
6. In case of cryogenic burn, rinse with plenty of water.
7. If clothing becomes saturated with oxygen, move away from the source of liquid oxygen and from places that present risks of inflammation, and remove such clothing.
8. Ventilate, if possible, the place of use, if it is reduced locations (vehicles, home)
9. Avoid exposure to heat sources or prolonged solar heating
10. Open the valve progressively
11. Close the valve of the container after its use
12. Never force any part of the container and do not attempt to repair a faulty valve.
13. Never exceed the maximum service pressure.
14. Provide safety devices against overpressure in liquid oxygen circuits where there is a risk of liquid accumulation between two valves.
15. Group the containers and keep them in a vertical position.
16. Use specific connections or flexible connection elements for oxygen.
17. Do not use intermediate connections to allow the connection of two devices that do not fit together.
18. In case of leakage, close the valve that has a leak and check that the emergency device is activated. Do not use a container with leaks
19. Use only equipment specifically approved for this product and for the pressure and temperature of use.
20. Do not allow the return of substances into the container. The entry of water into the container must be prevented.

This prospectus has been authorized in:

This information is intended only for healthcare professionals:

The dosage depends on the patient's clinical condition. The dose of oxygen should be adjusted according to the individual requirements of each patient and taking into account the risk of oxygen intoxication.

Oxygen therapy aims, in any case, to maintain an arterial partial pressure of oxygen (PaO2) above 60 mm Hg (i.e., 7.96 kPa) or an oxygen saturation in arterial blood above or equal to 90%,

If oxygen is administered diluted in another gas, its minimum concentration in the inhaled air must be 21%, i.e., the inspired fraction (Fi O2) must be 21%, and may reach a concentration of up to 100%.

Warnings and precautions for use

• In certain severe cases of hypoxia, the therapeutic dose approaches the threshold of toxicity. After 6 hours of exposure to an oxygen concentration of 100%, or after 24 hours of exposure to an oxygen concentration above 70%, pulmonary or neurological toxicity may appear.

• High concentrations should be used for the shortest possible time and controlled by analyzing the gases in arterial blood, while measuring the concentration of inhaled oxygen; it is advisable to use, in any case, the lowest dose capable of maintaining the arterial partial pressure of oxygen (Pa O2) at 50-60 mm Hg (i.e., at 5.65-7.96 kPa) and, after 24 hours of exposure, try to maintain, as far as possible, an oxygen concentration below 45%.

• In neonates and premature babies, it is necessary to use the lowest possible concentration that has the desired effect to minimize the risk of eye damage, retrolental fibroplasia, or other possible undesirable effects. For infants who need an oxygen concentration (Fi O2) above 30%, the Pa O2 concentration should be regularly controlled so that it does not exceed 100 mmHg (i.e., 13.3 kPa) due to the risk of alterations in the retina.

• Whenever oxygen is used, the increased risk of spontaneous ignition and fire must be taken into account. This risk increases when working with diathermy processes and defibrillation and electroconversion therapies.