MEDICAL LIQUID OXYGEN VIVISOL 99.5% MEDICINAL CRYOGENIC GAS

Introduction

Package Leaflet: Information for the User

Medicinal Liquid Oxygen VIVISOL 99.5% v/v, Cryogenic Medicinal Gas

Read the entire package leaflet carefully before starting to use this medication, as it contains important information for you.

• Keep this package leaflet, as you may need to read it again.
• If you have any questions, consult your doctor, pharmacist, or nurse.
• This medication has been prescribed to you only, and you should not give it to others, even if they have the same symptoms as you, as it may harm them.
• If you experience side effects, consult your doctor, pharmacist, or nurse, even if they are not listed in this package leaflet. See section 4.

Contents of the Package Leaflet

1. What is Medicinal Liquid Oxygen VIVISOL and what is it used for
2. What you need to know before starting to use Medicinal Liquid Oxygen VIVISOL
3. How to use Medicinal Liquid Oxygen VIVISOL
4. Possible side effects
5. Storage of Medicinal Liquid Oxygen VIVISOL
6. Package Contents and Additional Information

1. What is Medicinal Liquid Oxygen VIVISOL and what is it used for

Medicinal oxygen contains oxygen, which is essential for life. Oxygen therapy can be performed under normal pressure and high pressure.

Normal Pressure Oxygen Therapy(normobaric oxygen therapy)

Normal pressure oxygen therapy can be used to treat:

• Low oxygen concentrations in the blood or a specific organor to prevent them
• Cluster headaches(a specific type of headache that causes short but very severe crises on one side of the head)

High-Pressure Oxygen Therapy(hyperbaric oxygen therapy)

High-pressure oxygen therapy should only be administered by qualified healthcare professionals to avoid the risk of injury from strong pressure fluctuations. High-pressure oxygen therapy can be used to:

• Treat severe carbon monoxide poisoning(e.g., when the patient is unconscious)
• Treat gas embolismcaused by a sudden decrease in atmospheric pressure (decompression sickness)
• Treat obstructionin the heart or blood vessels caused by gas bubbles (aeroembolism)
• Supportive treatment in cases of bone lossafter radiation therapy

For supportive treatment in cases of tissue necrosisdue to infected wounds with gas-producing bacteria

2. What you need to know before starting to use Medicinal Liquid Oxygen VIVISOL

Do not use Medicinal Liquid Oxygen VIVISOL

Oxygen should not be used at pressures above atmospheric pressure (hyperbaric oxygen therapy) in cases of untreated or undrained pneumothorax. Pneumothorax occurs due to the accumulation of air in the thoracic cavity between the two lung membranes. If you have ever had pneumothorax, inform your doctor.

Warnings and Precautions

Consult your doctor or pharmacist before starting to use Medicinal Liquid Oxygen VIVISOL:

• Oxygen may have harmful effects at high concentrations. This could cause lung damage (alveolar collapse, inflammation of the lungs, which would obstruct the supply of oxygen to the blood).
• If you have chronic obstructive pulmonary disease (COPD) with resulting oxygen deficiency in the blood, the oxygen flow will be lower. Your doctor will adjust the oxygen therapy flow accordingly.
• Pay special attention when administering oxygen to newborns and premature babies. The reason is to minimize the risk of adverse events, such as eye damage. The lowest possible concentration of oxygen that is effective should be used to achieve adequate oxygenation.
• Pay special attention if your blood carbon dioxide levels have increased, as this neutralizes the effect of oxygen.
• If you have respiratory problems triggered by low oxygen levels in the blood, or if you are taking potent analgesics, close monitoring by your doctor will be necessary.
• If you have ever had lung injuries, inform your doctor.

Hyperbaric Oxygen Therapy

Before starting high-pressure oxygen therapy, inform your doctor if you have:

• Psychiatric problems(anxiety, psychosis)
• Claustrophobia(fear of enclosed spaces)
• Diabetes(high blood sugar levels); due to the risk of hypoglycemia, blood sugar levels should be measured between hyperbaric therapy sessions
• Respiratory disorders
• If you have ever had pneumothorax, which is an accumulation of air in the thoracic cavity between the two lung membranes
• Heart problems
• High blood pressure
• Eye problems
• Ear, nose, and throat disorders

Children

In premature and newborn babies, oxygen therapy can cause eye damage (retinopathy of prematurity). Your doctor will determine the appropriate oxygen concentration to administer to ensure your baby receives the correct treatment.

When using oxygen, there is a higher risk of fire ignition.

Using Medicinal Liquid Oxygen VIVISOL with other medications

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

If you are taking or have been prescribed bleomycin (to treat cancer), amiodarone (to treat heart disease), or nitrofurantoin (to treat infections), inform your doctor before using oxygen, as there is a possibility of toxic effects on the lungs.

Oxygen can exacerbate previous lung damage caused by the pesticide Paraquat. In case of Paraquat poisoning, additional oxygen administration should be avoided as much as possible.

Using Medicinal Liquid Oxygen VIVISOL with food, beverages, and alcohol

Do not consume alcoholwhile using this medication. Alcohol can cause respiratory depression.

Pregnancy, breastfeeding, and fertility

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

• During pregnancy, normal pressure oxygen therapy (normobaric oxygen therapy) is only allowed if necessary.
• There are no contraindications to using oxygen during the breastfeeding period.

High-pressure oxygen therapy (hyperbaric oxygen therapy) should only be used during pregnancy or if you think you may be pregnant if it is strictly necessary. Inform the treating doctor or specialist if this is the case.

Driving and using machines

Normal pressure medicinal oxygen (normobaric oxygen therapy) does not affect the ability to drive or use machines.

After receiving high-pressure oxygen therapy (hyperbaric oxygen therapy), you may experience visual and auditory disturbances that can affect your ability to drive and use machines.

3. How to use Medicinal Liquid Oxygen VIVISOL

Follow your doctor's instructions for administering this medication exactly. If in doubt, consult your doctor or pharmacist again.

Never change the concentration of oxygen administration or that of your child.

Dosage

Normal Pressure Oxygen Therapy(normobaric oxygen therapy)

• If the oxygen concentration in the blood or a specific organ is too low: Your doctor will indicate the duration and frequency of oxygen administration, as the dose may vary depending on each patient. The goal is always to use the lowest possible concentration of oxygen that is effective. However, the actual oxygen concentration for inhalation should never be less than 21% and can be increased up to 100%.
• To treat respiratory problemswhen oxygen levels are low in the blood (hypoxia) or as a respiratory stimulant(e.g., in lung diseases such as COPD):

The oxygen concentration will be maintained below 28% and sometimes below 24%. Oxygen concentrations for inhalation in newborns should be maintained below 40% and can only be increased up to 100% in very exceptional cases. The lowest possible concentration of oxygen that is effective should be used to achieve adequate oxygenation. It is recommended to avoid fluctuations in oxygen saturation.

• To treat cluster headaches:

100% oxygen is administered at a flow rate of 7 liters per minute for 15 minutes using a mask. Treatment should be started when the first symptoms occur.

How to use normal pressure oxygen therapy

• Medicinal oxygen is an inhalation gas administered with special equipment, such as a nasal catheter or mask. The excess oxygen leaves the body through exhalation and mixes with the ambient air (known as a "non-rebreathing" system).
• If you are unable to breathe on your own, you will be provided with artificial respiratory assistance. During anesthesia, special equipment with rebreathing or recycling systems is used so that the exhaled air is inhaled again (known as a "rebreathing" system).
• Oxygen can also be administered directly into the bloodstream using an "oxygenator" in cases such as cardiac surgery with a cardiopulmonary machine and other situations that require extracorporeal circulation.

How to receive high-pressure oxygen therapy

• High-pressure oxygen therapy should only be administered by healthcare professionals to avoid the risk of injury from strong pressure fluctuations.
• Depending on your situation, high-pressure oxygen therapy lasts between 45 and 300 minutes per session. Treatment may consist of one or two sessions, but long-term treatment can last up to 30 sessions or more, with several sessions per day if necessary.
• Oxygen therapy is administered in a special pressure chamber.
• High-pressure oxygen therapy can also be administered using a mask perfectly fitted to the face and a hood that covers the head or through a tube placed in the mouth.

If you use more Medicinal Liquid Oxygen VIVISOL than you should

In case of overdose, consult your doctor or pharmacist immediately or call the Toxicology Information Service, phone 91 562 04 20, indicating the medication and the amount inhaled.

The toxic effects of oxygen can vary depending on the oxygen pressure inhaled and the duration of exposure. At low pressure(0.5 to 2.0 bars), it is more likely that toxic effects will occur in the lungs (pulmonary area) than in the brain and spinal cord (central nervous system). At high pressure, the opposite occurs.

The effects on the lungs (pulmonary area) include respiratory difficulties, coughing, and chest pain.

The effects on the brain and spinal cord (central nervous system) include tinnitus, auditory and visual disturbances, nausea, dizziness, anxiety, and confusion, muscle cramps, localized (around the eyes, mouth, and forehead), fainting, and convulsions (epileptic seizures).

The ocular effects include blurred vision and reduced peripheral vision ("tunnel vision").

In case of oxygen intoxication due to hyperoxia, oxygen therapy should be reduced or, if possible, interrupted, and treatment of symptoms should be initiated.

If you forget to use Medicinal Liquid Oxygen VIVISOL

Use the oxygen as described in the dosage section of the package leaflet. Do not use a double dose to make up for the forgotten dose. This is because medicinal oxygen could be harmful at high concentrations.

If you stop using Medicinal Liquid Oxygen VIVISOL

Do not stop using this medication on your own initiative. Consult your doctor or pharmacist.

Safety measures for using medicinal oxygen

Oxygen is an oxidizing product and promotes combustion. There should be no smoking or open flames (e.g., pilot lights, stoves, ovens, gas chimneys, sparks, candles, etc.) in the rooms where medicinal oxygen is used, as this increases the risk of fire.

Handle the cylinder with care. Ensure that the gas cylinder does not suffer falls or is exposed to shocks.

If you have any further questions about the use of this medication, ask your doctor or pharmacist.

4. Possible side effects

Like all medications, this medication can cause side effects, although not everyone will experience them.

Very common(may affect more than 1 in 10 people)

With normobaric therapy: In newborns exposed to high oxygen concentrations: eye damage, which can cause vision problems.

With hyperbaric therapy: ear pain, myopia, barotrauma (injuries caused by changes in pressure).

Common(may affect up to 1 in 10 people)

With hyperbaric therapy: Convulsions

Uncommon(may affect up to 1 in 100 people)

With normobaric therapy: Lung collapse (atelectasis).

With hyperbaric therapy: Eardrum rupture

Rare(may affect up to 1 in 1,000 people)

With hyperbaric therapy: Shortness of breath, abnormally low blood sugar levels in diabetic patients.

Frequency not known(cannot be estimated from available data)

With normobaric therapy: Pulmonary toxicity, worsening of excess carbon dioxide in the blood (hypercapnia), dryness of the mucous membrane, local irritation, and inflammation of the mucosa.

With hyperbaric therapy: Difficulty breathing, involuntary muscle contractions, dizziness, hearing impairment, acute serous otitis, ringing or buzzing in the ears (tinnitus), nausea, abnormal behavior, reduced peripheral vision, visual changes, cataracts.

Reporting side effects

If you experience any side effects, consult your doctor or pharmacist, even if they are not listed in this package leaflet.

You can also report them directly through the Spanish Medicines Agency's online platform: www.notificaram.es

By reporting side effects, you can help provide more information on the safety of this medication.

5. Storage of Medicinal Liquid Oxygen VIVISOL

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

Do not use the medicinal oxygen after the expiration date stated on the gas cylinder/container/ tank, after the abbreviation EXP. The expiration date is the last day of the month indicated.

Medicinal Liquid Oxygen

Keep the container/tank in a well-ventilated area with a temperature range of -20°C and +50°C.

Keep it away from flammable and combustible materials, heat sources, or fires.

Do not smoke near the container/tank.

Transportation should be carried out in accordance with international regulations for transporting hazardous materials.

Avoid any contact with oils, fats, or hydrocarbons.

6. Container Content and Additional Information

Composition of Medicinal Liquid Oxygen VIVISOL

The active ingredient is oxygen, 100% v/v.

It does not contain any other active ingredients.

Product Appearance and Container Content

Medicinal oxygen is a gas for inhalation.

It is supplied in liquid form in a special container.

Oxygen is a colorless, odorless, and tasteless gas.

Liquid oxygen is blue in color.

Medicinal liquid oxygen:

Medicinal liquid oxygen is packaged in mobile cryogenic containers. The mobile cryogenic containers are manufactured with an outer and inner stainless steel container, with vacuum insulation panels between them, and equipped with a filling port and a tube retraction connection.

These containers contain oxygen in a liquid state at very low temperatures.

The content of the containers varies from 10 to 1000 liters.

Each liter of liquid oxygen supplies 853 liters of gaseous oxygen at 15°C and 1 bar.

Only some container sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

VIVISOL IBÉRICA, S.L.

C/ Yeso, 2

28500 Arganda del Rey (Madrid)

Spain

Manufacturer

Sol B S.R.L.

Zoning Ouest 15

7860 Lessines, Belgium

Or

VIVISOL IBÉRICA, S.L.

C/ Yeso, 2

28500 Arganda del Rey (Madrid)

Spain

Or

MESSER IBERICA DE GASES, S.A.

Autovia Tarragona-Salou, Km 3,800,

Vilaseca, 43480 Tarragona

Spain

Or

MESSER IBERICA DE GASES, S.A.

Pol. Industrial La Granadina III. C/Francia esquina C/Grecia Parcela 11.

San Isidro 03349 Alicante

Spain

Or

SOL FRANCE, SUCURSAL EN ESPAÑA

C/ del Telègraf 17-19, PI SOTA EL MOLI,

Montmeló, 08160 Barcelona

Date of the Last Revision of the Leaflet:September 2020.

This information is intended only for healthcare professionals:

Dosage

The concentration, flow, and duration of treatment must be determined by a doctor, according to the characteristics of each pathology.

Hypoxemia is a disorder in which the arterial partial pressure of oxygen (PaO2) is less than 10 kPa (<70 mmhg). an oxygen pressure level of 8 kpa (55 60 mmhg) leads to respiratory failure.< p>

Hypoxemia is treated by enriching the inhaled air with additional oxygen. The decision to introduce oxygen treatment depends on the degree of hypoxemia and the individual patient's tolerance level.

In all cases, the goal of oxygen treatment is to maintain a PaO2 > 60 mmHg (7.96 kPa) or an arterial oxygen saturation of ≥ 90%.

If oxygen is administered diluted in another gas, the oxygen concentration in the inhaled air (FiO2) must be at least 21%.

Normal pressure oxygen treatment (normobaric oxygen therapy):

Oxygen administration must be carried out with caution. The dose must be adapted to the individual needs of the patient, oxygen pressure must be maintained above 8.0 kPa (or 60 mmHg), and hemoglobin oxygen saturation must be > 90%. It is necessary to regularly monitor arterial oxygen pressure (PaO2) or pulse oximetry (arterial oxygen saturation [SpO2]) and clinical signs. The goal is for the inhaled air to always have the lowest effective oxygen concentration possible, which is the minimum dose to maintain a pressure of 8 kPa (60 mmHg)/saturation > 90%. The administration of high concentrations should be as brief as possible, under strict control of blood gas values.

Oxygen can be safely administered in the following concentrations and for the indicated periods:

Up to 100% for less than 6 hours.

60-70% for 24 hours.

40-50% during the second 24-hour period.

Oxygen is potentially toxic in concentrations above 40% after two days.

Neonates are not included in these guidelines because retrolental fibroplasia occurs with a much lower FiO2. To achieve adequate and appropriate oxygenation in neonates, the lowest effective concentrations should be selected.

• Patient with spontaneous breathing:

The effective oxygen concentration is at least 24%. Normally, a minimum of 30% oxygen is administered to ensure therapeutic concentrations with a safety margin.

Treatment with high oxygen concentration (> 60%) for short periods is indicated in cases of severe asthma crisis, pulmonary thromboembolism, pneumonia, pulmonary fibrosis, etc.

Low oxygen concentration is indicated for the treatment of patients with chronic respiratory failure caused by chronic obstructive respiratory disease or other causes. The oxygen concentration should not exceed 28%, and for some patients, even 24% may be excessive.

It is possible to administer higher oxygen concentrations (in some cases up to 100%), although it is very difficult to obtain concentrations > 60% (or 80% in the case of children) with the use of most administration devices.

The dose must be adapted to the individual needs of the patient, at flows ranging from 1 to 10 liters of gas per minute.

• Patient with chronic respiratory failure:

Oxygen should be administered at flows ranging from 0.5 to 2 liters/minute, and it is necessary to adjust the flow rate based on blood gas values. The effective oxygen concentration will be maintained below 28% and sometimes even below 24% in patients with respiratory disorders who depend on hypoxia as a respiratory stimulus.

• Chronic respiratory failure caused by chronic obstructive pulmonary disease (COPD) or other diseases.

Treatment is adjusted according to blood gas values. The arterial partial pressure of oxygen (PaO2) should be > 60 mmHg (7.96 kPa), and the arterial oxygen saturation should be ≥ 90%.

The most frequent administration rate is 1 to 3 liters/minute for 15 to 24 hours/day, which also includes paradoxical sleep (the most sensitive period to hypoxemia during the day). During a stable period of the disease, it is recommended to control CO2 concentrations twice every 3 or 4 weeks or 3 times a month, as CO2 concentrations may increase during oxygen administration (hypercapnia).

• Patient with acute respiratory failure:

Oxygen should be administered at a rate ranging from 0.5 to 15 liters/minute, and it is necessary to adjust the flow rate based on blood gas values. In emergency cases, patients with severe respiratory distress require considerably higher doses (up to 60 liters/minute).

• Patient with mechanical ventilation:

If oxygen is mixed with other gases, the fraction of oxygen in the inhaled gas mixture (FiO2) should not fall below 21%. In practice, 30% tends to be the lower limit. If necessary, the fraction of inhaled oxygen can be increased up to 100%.

• Pediatric population: Newborns:

In exceptional cases, concentrations of up to 100% can be administered to newborns, however, treatment should be closely monitored. The lowest effective concentrations should be used to achieve adequate oxygenation. As a general rule, oxygen concentrations above 40% in the inhaled air should be avoided, taking into account the risk of eye damage (retinopathy) or lung collapse. Arterial oxygen pressure should be closely monitored and maintained below 13.3 kPa (100 mmHg). Fluctuations in oxygen saturation should be avoided. By preventing substantial fluctuations in oxygenation, the risk of eye damage can be reduced. (See also section 4.4).

• Cluster headache:

In the case of cluster headache, 100% oxygen is administered at a flow rate of 7 liters/minute for 15 minutes through a well-fitting facial mask. Treatment should be started in the initial stage of the crisis.

Hypobaric oxygen treatment:

The doses and pressure must always be adapted to the patient's clinical picture, and treatment can only be administered after medical consultation. However, some recommendations based on current knowledge are as follows:

Hypobaric oxygen treatment is administered at pressures above 1 atmosphere (1.013 bar), between 1.4 and 3.0 atmospheres (normally between 2 and 3 atmospheres). Hypobaric oxygen is administered in a special pressurized room. Treatment with oxygen at elevated pressures can also be administered through a well-fitting facial mask with a hood that covers the head or through a tracheal tube.

Each treatment session lasts from 45 to 300 minutes, depending on the indication.

Sometimes, acute hypobaric oxygen treatment lasts only one or two sessions, while chronic treatment can last up to 30 sessions or more. If necessary, sessions can be repeated two or three times a day.

• Carbon monoxide poisoning:

If carbon monoxide poisoning occurs, oxygen should be administered as soon as possible in high concentrations (100%), until the carboxyhemoglobin concentration falls below dangerous levels (around 5%). Hyperbaric oxygen (from 3 atmospheres) is indicated in patients with acute CO poisoning or who have been exposed to intervals of ≥24 hours. Additionally, pregnant patients, patients with loss of consciousness, or those with higher carboxyhemoglobin levels justify hyperbaric oxygen treatment. Normobaric oxygen should not be used between multiple hyperbaric oxygen treatments, as it may contribute to toxicity. Hyperbaric oxygen also appears to have potential for deferred treatment of CO poisoning using multiple low-dose oxygen treatments.

• Patient with decompression sickness:

Fast treatment at 2.8 atmospheres is recommended, with up to 10 repetitions if symptoms persist.

• Patient with air embolism:

In this case, the doses are adapted to the patient's clinical picture and blood gas values. The target values are: PaO2 > 8 kPa or 60 mmHg, hemoglobin saturation > 90%.

• Patient with osteoradionecrosis:

Treatment of radiation lesions with hyperbaric oxygen typically consists of daily sessions of 90 to 120 minutes at 2.0 to 2.5 atmospheres for about 40 days.

• Patient with clostridial myonecrosis:

Treatment of 90 minutes at 3.0 atmospheres is recommended during the first 24 hours, followed by twice-daily treatments for 4 or 5 days, until clinical improvement is observed.

Method of Administration

Normobaric Oxygen Therapy

Oxygen is administered through the inhaled air, preferably with equipment designed for this purpose (e.g., a nasal catheter or mask). Through this equipment, oxygen is administered with the inhaled air. Subsequently, the gas and excess oxygen exit the patient with the exhaled air and mix with the ambient air (non-rebreathing system). In many cases, during anesthesia, special systems with a rebreathing or recycling system are used so that the exhaled air is inhaled again (rebreathing system).

If the patient is unable to breathe on their own, artificial respiratory assistance can be provided. On the other hand, oxygen can be injected directly into the bloodstream through the so-called oxygenator. The application of extracorporeal gas exchange devices facilitates oxygenation and decarboxylation without the damage associated with aggressive mechanical ventilation strategies. The oxygenator, which acts as an artificial lung, provides better oxygen transfer, and therefore, blood gas levels are maintained within clinically acceptable ranges. After recovery of lung function, the extracorporeal blood and gas flow are reduced and eventually stopped. This occurs, for example, during cardiac surgery using a cardiopulmonary bypass system, as well as in other circumstances that require extracorporeal circulation, including acute respiratory failure.

Hyperbaric Oxygen Therapy

Hyperbaric oxygen treatment is administered in a special pressurized room where the ambient pressure can be multiplied up to three times the atmospheric pressure. Hyperbaric oxygen treatment can also be administered through a well-fitting facial mask with a hood that covers the head or through a tracheal tube.

General

Medical gases should only be used for medical purposes.

Different types and qualities of gases should be separated from each other.

Full and empty containers should be stored separately.

Never use grease, oil, or similar substances to lubricate stuck or difficult-to-connect screw threads.

Handle valves and devices with clean hands and without any type of grease (hand cream, etc.).

Only use standard equipment designed for medicinal oxygen.

Preparation for Use

Only use dose administration devices designed for medicinal oxygen.

Check that the automatic coupling and administration device are clean and that the gaskets function properly. Never use pressure tools/regulators designed for manual connection, as this can damage the coupling.

Slowly open the valve: at least half a turn.

Check for leaks according to the instructions provided with the regulator.

In case of a leak, close the valve and disconnect the regulator. Mark the defective containers, store them separately, and return them to the supplier.

Use

It is strictly forbidden to smoke and start fires in the rooms where oxygen treatment is carried out.

If not in use or in case of fire, the device should be closed.

Take it to a safe place in case of fire.

Larger containers should be transported using specific vehicles for this purpose.

Pay special attention to connected devices so that they do not become disconnected accidentally.

When the container is empty, the gas flow will decrease. Close the outlet valve and remove the couplings after releasing the pressure.

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