Oxygen Sapio: detailed information

PACKAGE LEAFLET

Package leaflet: information for the patient

OXYGEN SAPIO 200 BAR COMPRESSED MEDICINAL GAS, CRYOGENIC MEDICINAL GAS

Oxygen
Please read this leaflet carefully before using this medicine because it contains important information for you.

Keep this leaflet. You may need to read it again.
If you have any questions, consult your doctor or pharmacist.
This medicine has been prescribed for you only. Do not give it to others, even if their symptoms are the same as yours, as it could be harmful.
If you experience any adverse reactions, including those not listed in this leaflet, consult your doctor or pharmacist. See section 4.

Contents of this leaflet:

What OXYGEN SAPIO is and what it is used for
What you need to know before using OXYGEN SAPIO
How to use OXYGEN SAPIO
Possible side effects
How to store OXYGEN SAPIO
Package contents and other information

1. What Ossigeno SAPIO is and what it is used for

Ossigeno SAPIO contains oxygen, a gas naturally present in the air we breathe.
Medical oxygen increases the delivery of oxygen to all tissues of the body.
Ossigeno SAPIO is indicated:
in the treatment of acute and chronic respiratory failure,
in anaesthesia,
in intensive care therapy,
in hyperbaric chamber treatment.

2. What you need to know before using Ossigeno SAPIO

You will not be administered Ossigeno SAPIO in a hyperbaric chamber if:

you suffer from a lung disease causing the formation of lung bubbles (bullous emphysema);
you suffer from progressive asthma;
you have a collapsed lung (pneumothorax);
you suffer from a chronic lung disease characterized by slow airway obstruction (chronic obstructive pulmonary diseases - COPD);
you have inflammation of the lungs (Pneumocystis carinii pneumonia);
you suffer from a condition characterized by uncontrollable body movements (epilepsy);
you have fear of enclosed spaces (claustrophobia);
you are in the first 3 months of pregnancy and do not have a serious illness;
you have a respiratory tract infection;
you have heat stroke (hyperthermia);
you suffer from a red blood cell disorder, a type of blood cell (hereditary spherocytosis);
you suffer from a disease of the optic nerve (optic neuritis);
you suffer from malignant tumors;
you have high levels of acid in the blood (acidosis);
you are taking medicines to treat tumors such as doxorubicin, adriamycin, daunorubicin, bleomycin, cisplatin (see section “Other medicines and Ossigeno SAPIO”);
you are taking medicines to treat inflammation such as corticosteroids (see section “Other medicines and Ossigeno SAPIO”);
you are taking a medicine to treat alcohol dependence (disulfiram) (see section “Other medicines and Ossigeno SAPIO”);
you consume alcohol;
you have recently been exposed to toxic substances (aromatic hydrocarbons);
you smoke or use nicotine-containing medicines to help quit smoking;
the newborn was born prematurely.

You must not use Ossigeno SAPIO
Under normal conditions, there are no absolute contraindications.
Warnings and precautions
Talk to your doctor or pharmacist before using Ossigeno SAPIO.
Inform your doctor:

if you are taking medicines to treat epilepsy (barbiturates) and/or pain (opioids);
if you have lung damage caused by a medicine called bleomycin (used for certain tumors);
if you have difficulty breathing due to certain diseases, e.g.: a chronic lung condition characterized by slow airway obstruction (chronic obstructive bronchopulmonary diseases - COPD), cystic fibrosis (a serious genetic disease), genetic overweight (pathological obesity), chest wall deformities, neuromuscular diseases (nervous system or muscle damage manifesting as reduced muscle strength or muscle paralysis), overdose of medicines causing severe breathing problems.

Your doctor will evaluate whether to administer hyperbaric chamber oxygen therapy if:

you suffer from inflammation of the ears and/or nose (recurrent otitis and/or sinusitis);
you suffer from heart disease (ischemic and/or congestive heart conditions);
you suffer from untreated high blood pressure (pharmacologically untreated arterial hypertension);
you suffer from lung diseases that prevent air passage (restrictive and/or severely restrictive pulmonary conditions);
you suffer from an eye disease characterized by high pressure of the fluid inside the eyes (glaucoma), or retinal detachment, a membrane of the eye;
you suffer from diabetes mellitus, as hyperbaric therapy may counteract insulin's effect and increase your blood sugar levels (hyperglycemia).

Safety precautions
During use

Do not use greasy creams or lipsticks.
Do not smoke.
Do not approach the container with open flames.
Do not use any electrical equipment that may produce sparks near patients receiving oxygen.
Do not use oils or greases on connectors, taps, valves, or any material in contact with oxygen.
Never introduce oxygen into a device that might contain materials capable of catching fire, especially fatty substances.

Children
In newborns, the doctor will administer the lowest effective oxygen concentration to avoid possible adverse effects that may occur following oxygen administration in newborns: vision defects (retinopathy), chronic lung diseases, bleeding within the brain (intraventricular hemorrhage).
Other medicines and Ossigeno SAPIO
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicine.
In particular, inform your doctor if you are taking:

catecholamines (e.g. epinephrine, norepinephrine), medicines that affect multiple body organs and are generally used to treat emergency situations of sudden allergic reactions;
corticosteroids (e.g. dexamethasone, methylprednisolone), medicines to treat inflammation;
hormones (e.g. testosterone, thyroxine);
amiodarone, a medicine to treat heart rhythm disorders;
chemotherapeutic agents (e.g. bleomycin, cyclophosphamide, 1,3-bis(2-chloroethyl)-1-nitrosourea) and adriamycin, medicines to treat tumors;
antimicrobial agents (e.g. nitrofurantoin), medicines to treat germ infestations;
antibiotics (e.g. actinomycin, nitrofurantoin), medicines to treat infections;
menadione-based supplements;
medicines to treat mental disorders (e.g. promazine, chlorpromazine, thioridazine);
chloroquine, a medicine to treat malaria.

Additionally, inform your doctor if:

you have recently undergone an X-ray examination;
you suffer from an overactive thyroid gland, a neck gland (hyperthyroidism);
you have vitamin C and/or E deficiency or a substance called glutathione (an antioxidant, i.e. one that counteracts aging);
you have undergone treatment for paraquat poisoning (a herbicide);
you consume alcohol.

Ossigeno SAPIO and alcohol
Do not consume alcohol during treatment with Ossigeno SAPIO.
Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, planning to become pregnant, or breastfeeding, consult your doctor or pharmacist before taking this medicine.
During pregnancy, Ossigeno SAPIO should be used only if absolutely necessary and after evaluation of the benefit-risk ratio by your doctor.
Ossigeno SAPIO is contraindicated during the first three months of pregnancy in a hyperbaric chamber.
The use of hyperbaric therapy during pregnancy may induce oxidative stress causing fetal harm. In cases of severe carbon monoxide poisoning, your doctor will assess the benefit-risk ratio.
Ossigeno SAPIO may be used during breastfeeding.
Driving and using machines
Ossigeno SAPIO does not affect or has a negligible effect on the ability to drive vehicles and use machinery.
If the medicine is administered in a hyperbaric chamber, visual and hearing disturbances may occur which could affect the ability to drive vehicles and use machinery. In this case, do not drive vehicles or operate machinery until symptoms have completely resolved.

3. How to use Oxygen SAPIO

Use this medicine exactly as directed by your doctor or pharmacist. If you have any doubts, consult your doctor.
Oxygen SAPIO is usually inhaled through the nose and mouth via a nasal cannula or a face mask; the dosage is administered using metering devices (flowmeters).
The dose will be determined by your doctor according to your health condition.
During treatment with Oxygen SAPIO, your doctor may perform measurements of arterial blood gases and monitor levels of oxygen bound to haemoglobin, a protein that carries oxygen in the blood.

Use in newborns
In newborns, the doctor will administer the lowest effective oxygen concentration to avoid potential adverse effects that may occur following oxygen administration in neonates (visual defects, chronic lung diseases, intracranial bleeding).

If you use more Oxygen SAPIO than you should
If you use more Oxygen SAPIO than you should, contact your doctor or go to hospital immediately.
Symptoms of overdose that you may experience are:

hyperoxia,
inflammation of the trachea and bronchi (tracheobronchitis),
interstitial edema,
pulmonary fibrosis.

Symptoms of overdose that you may experience following hyperbaric chamber therapy are:

ringing in the ears (tinnitus),
visual and hearing disturbances,
localized muscle spasms (particularly in eyes, mouth, forehead),
nausea, dizziness,
anxiety, confusion, irritability,
loss of consciousness,
uncontrolled body movements (convulsions).

In premature newborns, a high oxygen concentration may cause visual damage (retinopathy of prematurity).
If you are a patient at risk of respiratory failure, administration of supplemental oxygen may cause severe breathing problems (respiratory depression), increased blood acidity (respiratory acidosis), and reduced or stopped breathing (respiratory arrest).

Treatment
If high doses are used, your doctor will administer appropriate therapy and monitor you closely.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone experiences them.
Below are the side effects associated with Ossigeno SAPIO. There are insufficient data available to determine the frequency of the individual effects listed.
The tissues most sensitive to this medicine are the lungs, the brain, and the eyes.

Effects affecting respiration:

Inflammation of the trachea and bronchi (tracheobronchitis);
Chest pain;
Dry cough;
Atelectasis due to reduced nitrogen in the alveoli and the direct effect of oxygen on alveolar surfactant;
Mixing within the lung of carbon dioxide-rich blood with oxygen-rich blood (intrapulmonary shunt);
Worsening of respiratory problems in patients affected by respiratory depression induced by medicines (opioids, barbiturates) or by chronic obstructive bronchopulmonary diseases (COPD).

Effects affecting the nervous system:

Visual disturbances (blurred vision, reduced peripheral vision);
Ringing in the ears (tinnitus);
Respiratory disturbances;
Localized muscle spasms (particularly of the eyes, mouth, and forehead);
Dizziness and nausea;
Changes in behaviour (anxiety, confusion, irritability);
Decreased level of consciousness (up to loss of consciousness);
Side effects caused by excessive oxygen administration are reversible and do not cause any neurological damage, disappearing when the partial pressure of inspired oxygen is reduced.

Side effects related to hyperbaric oxygen therapy (hyperbaric oxygen therapy - HBOT):

Confinement anxiety (due to the relatively small size of some hyperbaric chambers, not to a direct effect of oxygen).

Effects related to ocular toxicity:

Progressive visual damage (progressive myopia) in cases of multiple hyperbaric treatments.

Side effects in children:

Lung diseases (bronchopulmonary dysplasia, pulmonary fibrosis, up to respiratory insufficiency). In newborns, and particularly in premature infants:
Temporary or permanent visual damage (retinopathy of prematurity) in newborns (especially premature infants) exposed to high oxygen concentrations or for prolonged periods.

Risk of burns

Thermal burns (the risk of fire increases in the presence of high oxygen concentrations and ignition sources);
Cold burns (in case of direct contact with liquid oxygen).

The following side effects (with their respective frequencies) are associated with normobaric oxygen therapy:
Eye disorders
Very common (may affect more than 1 in 10 people):

Temporary or permanent visual damage (retinopathy of prematurity) in newborns (especially premature infants) exposed to high oxygen concentrations or for prolonged periods.

Respiratory, thoracic and mediastinal disorders
Not known (frequency cannot be determined from available data):

Inflammation of the trachea and bronchi (tracheobronchitis);
Chest pain;
Dry cough;
Interstitial edema (swelling);
Pulmonary fibrosis;
Severe breathing problems (respiratory depression), increased blood acidity (respiratory acidosis), and cessation of breathing (respiratory arrest) in patients with long-term diseases associated with oxygen deficiency.

General disorders and administration site conditions
Not known (frequency cannot be determined from available data):

Dryness and irritation of the mucous membranes of the airways.

The following side effects (with their respective frequencies) are associated with hyperbaric oxygen therapy:

Respiratory, thoracic and mediastinal disorders
Rare (may affect up to 1 in 1,000 people):

Difficulty breathing (dyspnea).
Not known (frequency cannot be determined from available data):
Respiratory disturbances.

Nervous system disorders
Common (may affect up to 1 in 10 people):

Uncontrolled body movements (seizures).

Musculoskeletal and connective tissue disorders
Not known (frequency cannot be determined from available data), including:

Localized muscle spasms.

Ear and labyrinth disorders
Very common (may affect more than 1 in 10 people):

Ear pain.
Uncommon (may affect up to 1 in 100 people):
Perforation of the eardrum.
Not known (frequency cannot be determined from available data):
Vertigo;
Hearing loss;
Acute serous otitis media (acute infection of the middle ear in which a serous collection forms and becomes infected by bacteria or viruses originating from the nasopharynx);
Ringing in the ears (tinnitus).

Gastrointestinal disorders
Not known (frequency cannot be determined from available data):

Nausea.

Psychiatric disorders
Not known (frequency cannot be determined from available data):

Abnormal behaviour.

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

Progressive visual damage (progressive myopia) in cases of multiple hyperbaric treatments.

Side effects with unknown frequency (frequency cannot be determined from available data), including:

Visual disturbances (blurred vision, reduced peripheral vision);
Cataract.

Injury, poisoning and procedural complications
Very common (may affect more than 1 in 10 people):

Tissue injury caused by imbalance between the pressure of air contained in a body cavity and the pressure of the surrounding environment (barotrauma), which may manifest as ear pain and possible bleeding (with risk of swelling or rupture of the eardrum), damage to the paranasal sinuses, damage to the lungs, toothache.

Metabolism and nutrition disorders
Rare (may affect up to 1 in 1,000 people):

Hypoglycaemia (low blood sugar levels) in diabetic patients.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist, or nurse. You may also report side effects directly via the national reporting system at www.agenziafarmaco.gov.it/content/come-segnalare-una-sospetta-reazione-avversa.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Ossigeno SAPIO

Store cylinders and mobile cryogenic containers at temperatures between -10°C and 50°C.
Keep this medicinal product out of the sight and reach of children.
Do not use this medicinal product after the expiry date stated on the label after EXP. The expiry date refers to the last day of that month.
Do not dispose of any medicinal product in wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. This will help protect the environment.

6. Contents of the pack and other information

What Ossigeno SAPIO contains

The active substance is 100% oxygen

Description of the appearance of Ossigeno SAPIO and contents of the pack
Compressed medicinal gas
OSSIGENO SAPIO compressed medicinal gas is supplied in cylinders in compressed gaseous form at 200 bar and 15°C. The cylinders are made of steel or aluminium alloy and are equipped with valves compatible with pressure regulators or with integrated pressure-reducing valves.
Cryogenic medicinal gas
OSSIGENO SAPIO cryogenic medicinal gas is supplied in mobile cryogenic containers (base units).
Available pack sizes:
Compressed medicinal gas
Steel cylinders: 0.5, 1, 2, 3, 5, 7, 10, 14, 20, 27 litres; aluminium cylinders: 0.5, 1, 2, 3, 5, 7, 10, 14, 20 litres.
Steel cylinders with integrated pressure-reducing valve: 0.5, 1, 2, 3, 5, 7, 10, 14, 20, 27 litres; aluminium cylinders with integrated pressure-reducing valve: 0.5, 1, 2, 3, 5, 7, 10, 14 litres.
Cryogenic medicinal gas
Mobile cryogenic containers: 10, 21, 31, 32, 36, 41, 46, 160, 180, 230 litres.
Not all pack sizes may be commercially available.

Marketing Authorization Holder
SAPIO Produzione Idrogeno Ossigeno S.r.l
Via S. Maurilio, 13
Milan

Manufacturer
Compressed medicinal gas and cryogenic medicinal gas (mobile containers)
Sapio Produzione Idrogeno Ossigeno srl – Via De Amicis, 140 – 10093 Collegno (TO)
Sapio Produzione Idrogeno Ossigeno srl – Via Senatore Simonetta 27 – 20867 Caponago (MB)
Sapio Produzione Idrogeno Ossigeno srl – Corso Stati Uniti 21 – 35100 Padua (PD)
Sapio Produzione Idrogeno Ossigeno srl – Via P. Belizzi 77/79 – 29100 Piacenza (PC)
Sapio Produzione Idrogeno Ossigeno srl – Loc. Poggio Bagnoli – 52020 Pergine Valdarno (AR)
Sapio Produzione Idrogeno Ossigeno srl – Contrada Camera 90/A – 63023 Fermo (AP)
Sapio Produzione Idrogeno Ossigeno srl – Via Metaponto, 8700 – 74123 Taranto (TA)
Sapio Produzione Idrogeno Ossigeno srl – Località Passo Vecchio – 88074 Crotone (KR)
Sapio Produzione Idrogeno Ossigeno srl – Via Enrico Alberto D’Albertis 25 – 07046 Porto Torres (SS)
Puglia Life S.r.l. – Zona Industriale P.I.P. Lotto Nr. 5 – 72023 Mesagne (BR)
Oxygen Center Di Coluccia Giuseppina &C S.A.S. – Zona Artigianale – 73028 Otranto (LE)
Salentossigeno Srl – Via Veglie – Zona Artigianale – 73045 Leverano (LE)
Utengas srl – Via Marconi 56/58 – 24040 Comun Nuovo (BG)
Medical Gas Criogenici srl - Viale Delle Industrie, Snc - Zona Industriale ASI - 92021 Aragona (AG)
Oxyplus srl – Via Maremmana Inferiore km. 0,5 Fraz. Villa Adriana – 00019 Tivoli (RM)
Eubios srl – Via Linara 3 – 82030 Limatola (BN)
Oxy Live srl – Via Nuova del Bosco km. 2 – 80034 Marigliano (NA)
Giannitrapani srl – 1° Dorsale, 8 Z.I.R. – 91100 Trapani (TP)
Giannitrapani srl – Via Ugo La Malfa – Contrada Cutelli – 90014 Casteldaccia (PA)
CER Medical S.r.l. – Via Torretta, 13 – 40012 – Calderara di Reno (BO)
MEDICAIR CENTRO S.r.l. - Via della Magliana, 1098/1102 - 00100 - Rome (RM)
CRIOSERVICE SRL - Via Madre Teresa di Calcutta (loc. Zona Commerciale Signora Porzia) 74045 - Leverano (LE)
Cryogenic medicinal gas (mobile containers)
T.S.A. S.A.S. Di Piani Alessandro Jr. E C. – Via Ezio Vanoni S.N.C. – 23037 Tirano (SO)
Di Maio Carmine – Contrada San Cataldo – 87010 Castrovillari (CS)
Agenzia KAPPA SAS di Fiore Paola E C. - Contrada Gabella S.N.C.- 85050 – Tito (PZ)
SAPIO PLINI d.o.o. - Bukovžlak 107, Teharje, Celje, 3000, Slovenia

The following information is intended exclusively for physicians or healthcare professionals:
Precautions for use
Oxygen must be administered with caution, adjusted according to the individual patient's needs. The lowest effective dose that maintains arterial oxygen pressure at 8 kPa (60 mmHg) should be administered. Higher concentrations should be given for the shortest possible duration, with frequent monitoring of blood gas analysis.
Oxygen can be safely administered at the following concentrations and for the following durations:
Up to 100%: less than 6 hours
60–70%: 24 hours
40–50%: during the second 24-hour period.
Oxygen may become toxic after two days at concentrations exceeding 40%.
Low oxygen concentrations should be used in patients with respiratory failure whose respiratory drive is dependent on hypoxia. In these cases, treatment must be closely monitored by measuring arterial oxygen tension (PaO₂), or by pulse oximetry (arterial oxygen saturation – SpO₂) and clinical assessment.
High oxygen concentrations in inhaled air or gas reduce nitrogen concentration and partial pressure. This also reduces nitrogen concentration in tissues and alveoli. If oxygen is absorbed into the blood through the alveoli faster than it is replenished by ventilation, alveolar collapse (atelectasis) may occur. This may impair arterial blood oxygenation, as gas exchange does not occur despite adequate perfusion.
In patients with reduced sensitivity to arterial carbon dioxide pressure, high oxygen levels may cause carbon dioxide retention. In extreme cases, this may lead to carbon dioxide narcosis.
Patients at risk of hypercapnic respiratory failure:
Special precautions must be taken in patients with reduced sensitivity to arterial carbon dioxide pressure or at risk of hypercapnic respiratory failure ("hypoxic drive") (e.g. patients with chronic obstructive bronchopulmonary disease (COPD), cystic fibrosis, morbid obesity, thoracic wall deformities, neuromuscular disorders, or respiratory depressant drug overdose). Administration of supplemental oxygen may cause respiratory depression and increased PaCO₂, leading to symptomatic respiratory acidosis. In these patients, oxygen therapy must be carefully titrated; the target oxygen saturation may be lower than in other patients, and oxygen should be administered at low flow rates.
Special precautions in patients with bleomycin-induced lung injury
High-dose oxygen therapy may potentiate pulmonary toxicity, even years after the initial lung injury caused by bleomycin, and the target oxygen saturation may need to be lower than in other patients (see section “Other medicines and Ossigeno SAPIO”).
Paediatric population
Due to the newborn's increased sensitivity to supplemental oxygen, the lowest effective oxygen concentration should be administered to achieve adequate oxygenation in neonates.
In preterm and term neonates, increased PaO₂ may lead to retinopathy of prematurity (see section “Possible side effects”), chronic lung disease, and intraventricular haemorrhage. It is recommended to initiate resuscitation of term or near-term neonates with air rather than 100% oxygen. In preterm neonates, the optimal oxygen concentration and target are not precisely defined. If required, supplemental oxygen should be carefully monitored and guided by pulse oximetry.
Hyperbaric oxygen therapy (HBOT)
Administration of oxygen in a hyperbaric chamber must be carefully evaluated based on risk/benefit ratio in the following conditions:

Recurrent otitis and/or sinusitis, laryngocele, mastoid cavities, vestibular syndrome, hearing loss, and recent middle ear surgery
Ischaemic and/or congestive cardiac diseases; in patients with acute coronary syndrome or acute myocardial infarction requiring hyperbaric therapy (e.g. in CO poisoning), hyperbaric treatment must be performed cautiously due to potential hyperoxic vasoconstriction in the coronary circulation
Untreated arterial hypertension
Severe restrictive and/or highly restrictive pulmonary diseases
Glaucoma, retinal detachment (even if surgically treated) (compensation maneuvers)
History of seizures or epilepsy
Uncontrolled high fever
Severe anxiety, psychosis, claustrophobia

Patients with diabetes mellitus
Hyperbaric therapy may interfere with glucose metabolism. The vasoconstrictive effects of hyperbaric therapy may also impair subcutaneous insulin absorption, leading to hyperglycaemia.
Blood glucose monitoring between hyperbaric therapy sessions may be considered.
Respiratory disorders
Due to decompression at the end of a hyperbaric session, gas volume increases as chamber pressure decreases, potentially causing partial pneumothorax or worsening of underlying pneumothorax. In a patient with undrained pneumothorax, decompression may lead to tension pneumothorax.
Furthermore, considering the risk of gas expansion during decompression in hyperbaric therapy, the benefit/risk ratio must be carefully evaluated in patients with poorly controlled asthma, pulmonary emphysema, chronic obstructive bronchopulmonary disease (COPD), or recent thoracic surgery.
Special warnings

In a hyperoxic environment, oxygen may saturate clothing.
It is absolutely forbidden to touch frozen parts (for cryogenic containers).
Cylinders and mobile cryogenic containers must not be used if visibly damaged, suspected of damage, or exposed to extreme temperatures.
Only oxygen-compatible and appropriate equipment must be used for the specific container model.
Pliers or other tools must not be used to open or close the cylinder valve to prevent damage.
In case of leakage, the cylinder valve must be closed immediately if safe to do so. If the valve cannot be closed, the cylinder must be moved to a safe outdoor location to allow oxygen to escape freely.
Valves of empty cylinders must be kept closed.
Oxygen has a strong oxidizing effect and may react violently with organic substances. Therefore, special precautions are required for handling and storage of containers.
It is not permitted to vent pressurized gas.
Take special safety precautions when handling cryogenic containers to avoid cold burns. Wear appropriate protective clothing (gloves, goggles, loose clothing, and trousers covering shoes). If liquid oxygen contacts skin or eyes, wash the affected areas with abundant cold water or apply cold compresses; seek immediate medical assistance.

Dosage, method and duration of administration
With these systems, oxygen (compressed or cryogenic) is administered via inhaled air, preferably using dedicated devices (e.g. nasal catheter or facial mask); dosing is independent of the medicinal gas packaging and is regulated via dosing devices (flowmeters).
With these systems, oxygen is delivered through the inhaled air, while exhaled gas and excess oxygen exit the patient's inspiratory circuit and mix with the surrounding air (open system or anti-rebreathing system).
Normobaric oxygen therapy
Normobaric oxygen therapy refers to the administration of a gas mixture richer in oxygen than atmospheric air, i.e. with an inspired oxygen fraction (FiO₂) exceeding 21%, at a partial pressure between 0.21 and 1 atmosphere (0.213 and 1.013 bar).
In patients without respiratory failure, oxygen may be administered via spontaneous ventilation using nasal cannulae, nasopharyngeal catheters, or suitable masks.
In patients with respiratory failure or under anaesthesia, oxygen must be administered via assisted ventilation.
Oxygen cylinders contain gas under a pressure of approximately 200 bar. This high pressure is regulated by a pressure reducer and indicated on the pressure gauge. Multiplying the gauge reading by the cylinder's volume (in litres) gives the amount of oxygen remaining in the cylinder.
With spontaneous ventilation
Patients with chronic respiratory failure: administer oxygen at a flow rate of 0.5 to 2 litres/minute, adjustable according to blood gas analysis.
Patients with acute respiratory failure: administer oxygen at a flow rate of 0.5 to 15 litres/minute, adjustable according to blood gas analysis.
Hyperbaric oxygen therapy
Hyperbaric oxygen therapy refers to treatment with 100% oxygen at pressures 1.4 times higher than atmospheric pressure at sea level (1 atm = 101.3 kPa = 760 mmHg). For safety reasons, pressure in hyperbaric oxygen therapy should not exceed 3 atm.
Oxygen must be administered in a hyperbaric chamber.
Session duration in a hyperbaric chamber at a pressure of 2 to 3 atmospheres (i.e. between 2.026 and 3.039 bar) ranges from 60 minutes to 4–6 hours. These sessions may be repeated 2 to 4 times daily, depending on the patient's clinical condition.
Compression and decompression should be performed slowly according to standard procedures to avoid barotrauma to air-containing anatomical cavities communicating with the external environment.
Hyperbaric oxygen therapy must be administered by qualified personnel.
Overdose
In case of oxygen toxicity related to hyperoxia, oxygen therapy should be reduced or, if possible, discontinued, and symptomatic treatment initiated.
Instructions for use and handling
Medical oxygen cylinders, as well as cryogenic containers, are exclusively intended for containing/transporting oxygen for inhalation, for therapeutic use.
Cylinders and mobile cryogenic containers (Base Units) must be transported using appropriate means to protect them from impact and falling risks.
Strictly follow these instructions:

Carefully read the instruction and user manual of the container (packaging).
Ensure all equipment is in good condition.
Secure cylinders and base units in an upright position to prevent falls, protect containers from impact, and keep them at temperatures below 50°C, ensuring adequate ventilation/aeration of rooms where the product is used. Cylinders must be fitted with a protective cap/tulip to cover the valve.
Handle equipment with clean hands, free from grease or oil.
Lift and move cylinders and base units only using the appropriate trolley; never lift a cylinder by its valve.
Use connectors, connecting tubes, or flexible hoses specifically designed and compatible with oxygen.
Particular attention must be paid to securing pressure reducers to cylinders, if not already integrated into the container closure system, to prevent accidental breakage.
It is absolutely forbidden to modify in any way the delivery equipment and its accessories or components (OIL AND GREASE MAY SPONTANEOUSLY IGNITE ON CONTACT WITH OXYGEN).
Do not lubricate or attempt to repair defective valves/taps.
It is absolutely forbidden to handle equipment or components with hands, clothing, or face contaminated with grease, oil, creams, or ointments.
It is absolutely forbidden to touch frozen parts (for cryogenic containers).

General instructions for use
Cylinders equipped only with a shut-off valve

Remove the protective cap, if present
Ensure the delivery valve is closed
Remove the tamper-evident seal
Connect the pressure reducer to the cylinder valve and the corresponding flowmeter
Connect the humidifier/bubbler
Connect the cannula with mask or goggles to the humidifier
Slowly open the main valve until fully open
Adjust the flowmeter to the required flow rate (litres/minute)

Cylinders equipped with integrated pressure-reducing valve

Ensure the valve is closed
Remove the tamper-evident seal
Ensure the flow indicator is set to zero
Connect the humidifier/bubbler
Connect the cannula with mask or goggles to the humidifier
Slowly open the main valve until fully open
Adjust the flowmeter to the required flow rate (litres/minute)
Mobile cryogenic containers
Ensure the flow indicator is set to zero
Remove the tamper-evident seal
Connect the humidifier/bubbler
Connect the cannula with mask or goggles to the humidifier
Set the flow regulator to the required flow rate (litres/minute)

NOTE: FOR FURTHER DETAILS, CONSULT THE USER MANUAL OF THE
CONTAINER
ATTENTION

Open container closure systems (valve or tap) gradually to avoid pressure surges.
Do not force taps or valves during opening or closing.
Never position yourself in front of the gas outlet of the tap/valve, but always on the opposite side. Do not expose yourself or the patient to direct gas flow.
Do not use oil or grease in contact with the gas.
Do not completely empty the container.
After use, close the cylinder tap.
In case of gas leakage, close the tap and contact the technical service of the supplier indicated on the container's user manual.
Use only containers suitable for the product and for the intended pressure and temperature conditions.

Disposal

Store empty cylinders with valves closed.
Do not discharge into sewers, basements, or pits where accumulation may be hazardous.
Return empty or unused containers, even if only partially empty, to the supplier. Any residual medicinal product remaining in the pressurized cylinder will be safely eliminated, via appropriate procedures, in a well-ventilated area by the company responsible for subsequent refilling of the container.

Observe all relevant rules for the use and handling of pressurized cylinders and containers containing cryogenic liquids.
Store cylinders and mobile cryogenic containers at temperatures between -10°C and 50°C, in well-ventilated areas or ventilated sheds, avoiding formation of hyperoxic atmospheres (O₂ > 21% vol), in an upright position with valves closed and protected from rain and weather, direct sunlight, heat sources, or ignition sources, and away from combustible materials. Empty containers or those containing other types of gases must be stored separately.

Package leaflet: information for the patient

OXYGEN SAPIO 200 BAR MEDICINAL COMPRESSED GAS, CRYOGENIC MEDICINAL GAS

Oxygen
Please read this leaflet carefully before you are administered this medicine, as it contains important information for you.

Keep this leaflet. You may need to read it again.
If you have any questions, ask your doctor, pharmacist, or nurse.
If you experience any side effects, including those not listed in this leaflet, inform your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet:

What OXYGEN SAPIO is and what it is used for
What you need to know before you are administered OXYGEN SAPIO
How OXYGEN SAPIO will be administered to you
Possible side effects
How to store OXYGEN SAPIO
Contents of the pack and other information

1. What Ossigeno SAPIO is and what it is used for

Ossigeno SAPIO contains oxygen, a gas naturally present in the air we breathe.
Medical oxygen increases oxygen delivery to all body tissues.
Ossigeno SAPIO is indicated:

in the treatment of acute and chronic respiratory insufficiency,
in anaesthesia,
in intensive care therapy,
in hyperbaric chamber treatment.

2. What you need to know before you are given Ossigeno SAPIO

You must not be given Ossigeno SAPIO in a hyperbaric chamber if:

you suffer from a lung disease causing air bubbles to form in the lungs (bullous emphysema);
you suffer from severe asthma;
you have a collapsed lung (pneumothorax);
you suffer from a chronic lung condition characterized by slow obstruction of the airways (chronic obstructive pulmonary disease - COPD);
you suffer from lung inflammation (Pneumocystis carinii pneumonia);
you suffer from a disease characterized by uncontrolled body movements (epilepsy);
you have fear of enclosed spaces (claustrophobia);
you are in the first 3 months of pregnancy and do not have a serious illness;
you have an upper respiratory tract infection;
you have heat stroke (hyperthermia);
you suffer from a red blood cell disorder, a type of blood cell (hereditary spherocytosis);
you suffer from a disease of the optic nerve (optic neuritis);
you suffer from malignant tumors;
you suffer from high levels of acid in the blood (acidosis);
you are taking medicines to treat tumors such as doxorubicin, adriamycin, daunorubicin, bleomycin, cisplatin (see section “Other medicines and Ossigeno SAPIO”);
you are taking medicines to treat inflammation such as corticosteroids (see section “Other medicines and Ossigeno SAPIO”);
you are taking a medicine to treat alcohol dependence (disulfiram) (see section “Other medicines and Ossigeno SAPIO”);
you consume alcohol;
you have recently been exposed to toxic substances (aromatic hydrocarbons);
you smoke or use nicotine-containing medicines to help people stop smoking;
the newborn was premature.

Warnings and precautions
Talk to your doctor or pharmacist before you are given Ossigeno SAPIO.
Inform your doctor if:

you are taking medicines to treat epilepsy (barbiturates) and/or pain (opioids).

Your doctor will evaluate whether to administer hyperbaric chamber oxygen if:

you suffer from inflammation of the ears and/or nose (recurrent otitis and/or sinusitis);
you suffer from a heart disease (ischemic and/or congestive heart diseases);
you suffer from high blood pressure and are not taking medication for it (untreated arterial hypertension);
you suffer from lung diseases that restrict airflow (restrictive and/or severely restrictive pulmonary diseases);
you suffer from an eye disease characterized by high pressure of the fluid inside the eyes (glaucoma), or from retinal detachment, a membrane of the eye;
you suffer from diabetes mellitus, as hyperbaric therapy may counteract the effect of insulin and increase your blood sugar levels (hyperglycemia).

Safety precautions
During use

Do not use greasy creams or lipsticks.
Do not smoke.
Do not bring open flames near the container.
Do not use any electrical equipment that may produce sparks near patients receiving oxygen.
Do not use oils or greases on connectors, taps, valves, or any material in contact with oxygen.
Never introduce oxygen into a device that might contain materials capable of catching fire, especially fatty substances.

Other medicines and Ossigeno SAPIO
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicine.
In particular, inform your doctor if you are taking:

catecholamines (e.g. epinephrine, norepinephrine), medicines that affect multiple organs and are generally used for emergency treatment of sudden allergic reactions;
corticosteroids (e.g. dexamethasone, methylprednisolone), medicines used to treat inflammation;
hormones (e.g. testosterone, thyroxine);
amiodarone, a medicine used to treat heart rhythm disorders;
chemotherapeutic agents (e.g. bleomycin, cyclophosphamide, 1,3-bis(2-chloroethyl)-1-nitrosourea) and adriamycin, medicines used to treat tumors;
antimicrobial agents (e.g. nitrofurantoin), medicines used to treat microbial infections;
antibiotics (e.g. actinomycin, nitrofurantoin), medicines used to treat infections;
menadione-based supplements;
medicines used to treat mental disorders (e.g. promazine, chlorpromazine, thioridazine);
chloroquine, a medicine used to treat malaria.

Additionally, inform your doctor if:

you have recently undergone an X-ray examination;
you suffer from a thyroid gland disorder in the neck causing overactivity (hyperthyroidism);
you have a deficiency in vitamin C and/or E or in a substance called glutathione (an antioxidant, i.e. one that counteracts aging);
you have undergone treatment for paraquat poisoning (a herbicide);
you consume alcohol.

Ossigeno SAPIO and alcohol
Do not consume alcohol during treatment with Ossigeno SAPIO.
Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, planning a pregnancy, or breastfeeding, consult your doctor or pharmacist before taking this medicine.
Ossigeno SAPIO is contraindicated during the first three months of pregnancy when administered in a hyperbaric chamber.
The use of hyperbaric therapy during pregnancy may induce oxidative stress with potential harm to the fetus. In cases of severe carbon monoxide poisoning, your doctor will assess the benefit-risk balance.
Ossigeno SAPIO may be used during breastfeeding.
Driving and using machines
Ossigeno SAPIO does not alter or alters only negligibly the ability to drive and use machines.
However, if the medicine is administered in a hyperbaric chamber, visual and hearing disturbances may occur that could affect your ability to drive and use machines. In such cases, do not drive or operate machinery until symptoms have completely resolved.

3. How Ossigeno SAPIO will be administered to you

This medicine will be administered to you via inhaled air, always strictly following the instructions of your doctor or nurse. If you have any doubts, consult your doctor.
Ossigeno SAPIO is usually inhaled through the nose and mouth using a nasal cannula or a mask. The dosage is controlled using dosing devices (flowmeters).
The dose will be determined by your doctor based on your health condition.
During treatment with Ossigeno SAPIO, your doctor may perform measurements of arterial blood gases and monitor levels of oxygen bound to haemoglobin, a protein that carries oxygen in the blood.

If you are given more Ossigeno SAPIO than you should receive
It is highly unlikely that you will receive more Ossigeno SAPIO than required, as your doctor or nurse will monitor you throughout treatment.
Symptoms of excessive dosage that you may experience are:

hyperoxia,
inflammation of the trachea and bronchi (tracheobronchitis),
interstitial edema,
pulmonary fibrosis.

Symptoms of excessive dosage that may occur following hyperbaric chamber therapy are:

ringing in the ears (tinnitus),
visual and hearing disturbances,
localized muscle spasms (particularly in eyes, mouth, forehead),
nausea, dizziness,
anxiety, confusion, irritability,
loss of consciousness,
uncontrolled body movements (convulsions).

In premature infants, a high oxygen concentration may cause visual damage (retinopathy of prematurity).
If you are a patient at risk of respiratory insufficiency, administration of supplemental oxygen may cause serious breathing problems (respiratory depression), increased blood acidity (respiratory acidosis), and reduced or stopped breathing (respiratory arrest).

Treatment
If you are given high doses, your doctor will provide appropriate therapy and monitor you closely.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone experiences them.
Below are the adverse effects of Ossigeno SAPIO. There are insufficient data available to determine the frequency of the individual effects listed.
The tissues most sensitive to this medicine are the lungs, brain, and eyes.

Effects affecting respiration:

inflammation of the trachea and bronchi (tracheobronchitis);
chest pain;
dry cough;
atelectasis due to decreased nitrogen in the alveoli and the direct effect of oxygen on alveolar surfactant;
mixing within the lung of carbon dioxide-rich blood with oxygen-rich blood (intralung shunt);
worsening of respiratory problems in patients affected by respiratory depression induced by medicines (opioids, barbiturates) or chronic obstructive bronchopulmonary diseases (COPD).

Effects affecting the nervous system:

visual disturbances (blurred vision, decreased peripheral vision);
ringing in the ears (tinnitus);
respiratory disturbances;
localized muscle spasms (particularly of the eyes, mouth, and forehead);
dizziness and nausea;
behavioral changes (anxiety, confusion, irritability);
decreased level of consciousness (up to loss of consciousness);
adverse effects caused by excessive oxygen administration are reversible and do not cause any neurological damage, disappearing when the partial pressure of inspired oxygen is reduced.

Adverse effects related to oxygen therapy in a hyperbaric chamber (hyperbaric oxygen therapy - HBOT):

confinement anxiety (due to the relatively small size of some hyperbaric chambers, not to a direct effect of oxygen).

Effects related to ocular toxicity:

progressive visual damage (progressive myopia) in cases of multiple hyperbaric treatments.

Adverse effects in children:

lung diseases (bronchopulmonary dysplasia, pulmonary fibrosis, up to respiratory insufficiency). In newborns, and particularly in premature infants:
temporary or permanent visual damage (retinopathy of prematurity) in newborns (especially premature ones) exposed to high oxygen concentrations or for prolonged periods;

Risk of burns

thermal burns (the risk of fire increases in the presence of high oxygen concentrations and ignition sources);
cold burns (in case of direct contact with liquid oxygen).

The following adverse effects (with their respective frequencies) are associated with normobaric oxygen therapy:
Eye disorders
Very common (may affect more than 1 in 10 people):

temporary or permanent visual damage (retinopathy of prematurity) in newborns (especially premature ones) exposed to high oxygen concentrations or for prolonged periods;

Respiratory, thoracic and mediastinal disorders
Not known (frequency cannot be determined from the available data):

inflammation of the trachea and bronchi (tracheobronchitis);
chest pain;
dry cough;
interstitial edema;
pulmonary fibrosis;
severe respiratory problems (respiratory depression), increased blood acidity (acidosis)

respiratory depression) and	cessation of breathing
terms associated with oxygen deficiency.		.

respiratory) and cessation of breathing (respiratory arrest) in patients with chronic respiratory diseases.

Systemic disorders and conditions related to the site of administration
Not known (frequency cannot be estimated from the available data):

dryness and irritation of the airway mucous membranes.

The following adverse reactions (with their respective frequencies) are associated with hyperbaric oxygen therapy:

Respiratory, thoracic and mediastinal disorders
Rare (may affect up to 1 in 1,000 people):

difficulty breathing (dyspnoea);
Not known (frequency cannot be estimated from the available data):
respiratory disorders.

Nervous system disorders
Common (may affect up to 1 in 10 people):

uncontrolled body movements (convulsions).

Musculoskeletal and connective tissue disorders
Not known (frequency cannot be estimated from the available data):

localized muscle spasms.

Ear and labyrinth disorders
Very common (may affect more than 1 in 10 people):

ear pain.
Uncommon (may affect up to 1 in 100 people):
perforation of the tympanic membrane.
Not known (frequency cannot be estimated from the available data):
vertigo;
hearing loss;
acute serous otitis media (acute infection of the middle ear with accumulation of serous fluid which becomes infected by bacteria or viruses coming from the nasopharynx);
ringing in the ears (tinnitus).

Gastrointestinal disorders
Not known (frequency cannot be estimated from the available data):

nausea.

Psychiatric disorders
Not known (frequency cannot be estimated from the available data):

abnormal behaviour.

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

progressive visual damage (progressive myopia) in cases of multiple hyperbaric treatments;
Not known (frequency cannot be estimated from the available data), including:
visual disturbances (blurred vision, decreased peripheral vision);
cataract.

Injury, poisoning and procedural complications
Very common (may affect more than 1 in 10 people):

tissue injury caused by imbalance between the air pressure within a body cavity and the surrounding environmental pressure (barotrauma), which may manifest as ear pain and possible ear bleeding (with risk of swelling or rupture of the tympanic membrane), damage to the paranasal sinuses, lung damage, toothache.

Metabolism and nutrition disorders
Rare (may affect up to 1 in 1,000 people):

hypoglycaemia (low blood sugar levels) in diabetic patients.

Reporting of adverse reactions
If you experience any adverse reaction, including those not listed in this leaflet, please inform your doctor, pharmacist or nurse. You can also report adverse reactions directly via the national reporting system at the website: www.agenziafarmaco.gov.it/content/come-segnalare-una-sospetta-reazione-avversa.
By reporting adverse reactions, you can help provide more information on the safety of this medicine.

5. How to store Ossigeno SAPIO

Store cylinders and mobile cryogenic containers at temperatures between -10°C and 50°C.
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the label after EXP. The expiry date refers to the last day of that month.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package Contents and Other Information

What Ossigeno SAPIO Contains

The active substance is 100% oxygen.

Description of the Appearance of Ossigeno SAPIO and Contents of the Package
Compressed medicinal gas
Ossigeno SAPIO compressed medicinal gas is supplied in cylinders and cylinder packs, in the form of compressed gas at 200 bar at 15°C.
The cylinders are made of steel or aluminum alloy and are equipped with valves suitable for connection to a pressure reducer.

Cryogenic medicinal gas
Ossigeno SAPIO cryogenic medicinal gas is supplied in fixed cryogenic containers.
Available pack sizes:
Compressed medicinal gas
Steel cylinders of 40 and 50 litres. Cylinder packs containing 12, 16, or 20 cylinders of 40 litres; cylinder packs containing 12 or 16 cylinders of 50 litres; cylinder packs containing 16 cylinders of 60 litres.

Cryogenic medicinal gas
Fixed cryogenic containers of 1000, 1500, 2000, 2500, 3000, 4000, 5000, 6000, 10000, 12000, 15000, 20000, 30000, and 40000 litres.
Not all pack sizes may be commercially available.

Marketing Authorization Holder
SAPIO PRODUZIONE IDROGENO OSSIGENO S.R.L
Via S. Maurilio, 13
Milan

Manufacturer
Compressed medicinal gas
Sapio Produzione Idrogeno Ossigeno srl – Via De Amicis, 140 – 10093 Collegno (TO)
Sapio Produzione Idrogeno Ossigeno srl – Via Senatore Simonetta 27 – 20867 Caponago (MB)
Sapio Produzione Idrogeno Ossigeno srl – Corso Stati Uniti 21 – 35100 Padova (PD)
Sapio Produzione Idrogeno Ossigeno srl – Via P. Belizzi 77/79 – 29100 Piacenza (PC)
Sapio Produzione Idrogeno Ossigeno srl – Loc. Poggio Bagnoli – 52020 Pergine Valdarno (AR)
Sapio Produzione Idrogeno Ossigeno srl – Contrada Camera 90/A – 63023 Fermo (AP)
Sapio Produzione Idrogeno Ossigeno srl – Via Metaponto, 8700 – 74123 Taranto (TA)
Sapio Produzione Idrogeno Ossigeno srl – Località Passo Vecchio – 88074 Crotone (KR)
Sapio Produzione Idrogeno Ossigeno srl – Via Enrico Alberto D’Albertis 25 – 07046 Porto Torres (SS)
Puglia Life S.r.l. – Zona Industriale P.I.P. Lotto Nr. 5 – 72023 Mesagne (BR)
Oxygen Center Di Coluccia Giuseppina &C S.A.S. – Zona Artigianale – 73028 Otranto (LE)
Salentossigeno Srl – Via Veglie – Zona Artigianale – 73045 Leverano (LE)
Utengas srl – Via Marconi 56/58 – 24040 Comun Nuovo (BG)
Medical Gas Criogenici srl - Viale Delle Industrie, Snc - Zona Industriale ASI - 92021 Aragona (AG)
Oxyplus srl – Via Maremmana Inferiore km. 0,5 Fraz. Villa Adriana – 00019 Tivoli (RM)
Eubios srl – Via Linara 3 – 82030 Limatola (BN)
Oxy Live srl – Via Nuova del Bosco km. 2 – 80034 Marigliano (NA)
Giannitrapani srl – 1° Dorsale, 8 Z.I.R. – 91100 Trapani (TP)
Giannitrapani srl – Via Ugo La Malfa – Contrada Cutelli – 90014 Casteldaccia (PA)
CER Medical S.r.l. – Via Torretta, 13 – 40012 Calderara di Reno (BO)
MEDICAIR CENTRO S.r.l. - Via della Magliana, 1098/1102 - 00100 - Roma (RM)
CRIOSERVICE SRL - Via Madre Teresa di Calcutta (loc. Zona Commerciale Signora Porzia) 74045 - Leverano (LE)

Cryogenic medicinal gas (fixed containers)
Air Liquide Italia Produzione srl – Via Industrie, 28 – 37014 – Castelnuovo del Garda (VR)
Air Liquide Italia Produzione srl – Via Vigonovese, 79 – 35100 – Padova
Air Liquide Italia Produzione srl – Via Dante s.n.c. – 20090 – Pioltello (MI)
Air Liquide Italia Produzione srl – Contrada Biggemi ex S.S. 114 – 96010 – Priolo Gargallo (SR)
Chemgas srl – Via E. Fermi – 72100 – Brindisi
Linde Gas Italia srl – Via Turati, 18/a – 40010 – Sala Bolognese (BO)
Linde Gas Italia srl – Via di Servola, 1 – 34100 – Trieste
Rivoira Operations S.r.l. – Via Baiona, 107/111 – 48100 – Ravenna
Rivoira Operations S.r.l. – Via Glair, 30 – 11029 – Verres (AO)
Società Italiana Acetilene & Derivati "S.I.A.D." SpA – S.S. del Brembo, 1 – 24040 – Osio Sopra (BG)
Sol Gas Primari S.r.l. – Via Firmio Leonzio, 2 – 84100 – Salerno
SICO Società Italiana Carburo Ossigeno SpA – Via Marconato s.n.c. – 20031 – Cesano Maderno (MB)
Sapio Produzione Idrogeno Ossigeno srl – Via Senatore Simonetta, 27 – 20867 – Caponago (MB)
Sapio Produzione Idrogeno Ossigeno srl – Via Malcontenta, 49 (locality Porto Marghera) – 30175 – Venice
Sapio Produzione Idrogeno Ossigeno S.r.l. – Località Caldare, s.n.c. – 01028 – Orte (VT)
Medical Gas Criogenici S.r.l. – Viale delle Industrie, SNC – Zona Industriale ASI – 92021 Aragona (AG)
MEDICAIR ITALIA S.R.L. Contrada S. Benedetto - Zona ASI – 92026 – FAVARA (AG)

The following information is intended exclusively for physicians or healthcare professionals:
Precautions for Use
Oxygen must be administered with caution, with adjustments based on the individual patient's needs. The lowest effective dose that maintains arterial oxygen pressure at 8 kPa (60 mmHg) should be administered. Higher concentrations should be given for the shortest possible duration, with frequent monitoring of blood gas analysis values.

Oxygen can be safely administered at the following concentrations and for the following durations:
Up to 100%: less than 6 hours
60–70%: up to 24 hours
40–50%: during the second 24-hour period.
Oxygen is potentially toxic after two days at concentrations above 40%.

Low oxygen concentrations should be used in patients with respiratory insufficiency in whom the respiratory drive is stimulated by hypoxia. In these cases, treatment must be closely monitored by measuring arterial oxygen tension (PaO₂), or by pulse oximetry (arterial oxygen saturation – SpO₂) and clinical assessment.

High oxygen concentrations in inhaled air or gas reduce nitrogen concentration and pressure. This also reduces nitrogen levels in tissues and alveoli. If oxygen is absorbed into the blood through the alveoli faster than it is replenished by ventilation, alveolar collapse (atelectasis) may occur. This may impair arterial blood oxygenation, as gas exchange cannot occur despite adequate perfusion.

In patients with reduced sensitivity to arterial carbon dioxide pressure, high oxygen levels may cause carbon dioxide retention. In extreme cases, this may lead to carbon dioxide narcosis.

Patients at risk of hypercapnic respiratory failure:
Special precautions must be taken in patients with reduced sensitivity to arterial carbon dioxide pressure or at risk of hypercapnic respiratory failure ("hypoxic drive") (e.g., patients with chronic obstructive bronchopulmonary disease (COPD), cystic fibrosis, morbid obesity, thoracic wall deformities, neuromuscular disorders, or respiratory depressant drug overdose). Administration of supplemental oxygen may cause respiratory depression and increased PaCO₂, leading to symptomatic respiratory acidosis. In these patients, oxygen therapy must be carefully titrated; the target oxygen saturation may be lower than in other patients, and oxygen should be administered at low flow rates.

Special precautions in patients with bleomycin-induced lung injury
Pulmonary toxicity from high-dose oxygen therapy may exacerbate lung injury, even years after the initial lung damage caused by bleomycin. The target oxygen saturation in these patients may need to be lower than in others (see section “Other medicines and Ossigeno SAPIO”).

Paediatric population
Due to the newborn's increased sensitivity to supplemental oxygen, the lowest effective oxygen concentration should be administered to achieve adequate oxygenation in neonates.

In preterm and term neonates, increased PaO₂ may lead to retinopathy of prematurity (see section “Possible side effects”), chronic lung disease, and intraventricular haemorrhage. It is recommended to initiate resuscitation of term or near-term neonates with air rather than 100% oxygen. In preterm neonates, the optimal oxygen concentration and target are not precisely defined. If supplemental oxygen is required, it should be carefully monitored and guided by pulse oximetry.

Hyperbaric Oxygen Therapy (HBOT)
Administration of oxygen in a hyperbaric chamber must be carefully evaluated based on the benefit-risk ratio in the following conditions:

Recurrent otitis and/or sinusitis, laryngocele, mastoid cavities, vestibular syndrome, hearing loss, and recent middle ear surgery
Ischemic and/or congestive cardiac diseases; in patients with acute coronary syndrome or acute myocardial infarction requiring hyperbaric therapy (e.g., in cases of CO poisoning), hyperbaric therapy should be performed cautiously due to potential hyperoxic vasoconstriction in the coronary circulation
Untreated arterial hypertension
Severe restrictive and/or obstructive lung diseases
Glaucoma, retinal detachment (even if surgically treated) (compensation maneuvers)
History of seizures, epilepsy
Uncontrolled high fever
Severe anxiety, psychosis, claustrophobia

Respiratory disorders
Due to decompression at the end of a hyperbaric session, gas volume increases as chamber pressure decreases, potentially causing partial pneumothorax or worsening of underlying pneumothorax. In a patient with undrained pneumothorax, decompression may lead to tension pneumothorax.

Furthermore, considering the risk of gas expansion during decompression in hyperbaric therapy, the benefit-risk ratio must be carefully assessed in patients with poorly controlled asthma, pulmonary emphysema, chronic obstructive bronchopulmonary disease (COPD), or recent thoracic surgery.

Special Warnings

In a hyperoxygenated environment, oxygen may saturate clothing.
Contact with frozen parts (for cryogenic containers) is strictly prohibited.
Cylinders must not be used if visibly damaged or if damage is suspected, or if they have been exposed to extreme temperatures.
Only oxygen-compatible and suitable equipment for the specific container model may be used.
Pliers or other tools must not be used to open or close the cylinder valve to prevent damage.
In case of leakage, the cylinder valve must be closed immediately, if safe to do so. If the valve cannot be closed, the cylinder must be moved to a safe outdoor location to allow oxygen to escape freely.
Valves of empty cylinders must remain closed.
Oxygen has a strong oxidizing effect and may react violently with organic substances. Therefore, special precautions are required when handling and storing containers.
Pressurized gas administration is not permitted.
Take special safety precautions when handling cryogenic containers to avoid cold burns. Wear appropriate protective clothing (gloves, goggles, loose clothing, and pants covering shoes). If liquid oxygen contacts skin or eyes, wash affected areas with abundant cold water or apply cold compresses; seek immediate medical attention.

Dosage, Method, and Duration of Administration
Oxygen (compressed or cryogenic) is administered via the inspired air, while exhaled gas and excess oxygen exit the patient's inspiratory circuit and mix with ambient air (open system or anti-rebreathing system).

In anaesthesia, a special system is often used that allows rebreathing of previously exhaled gas (closed system or rebreathing system).

Oxygen may also be administered directly into the blood via an oxygenator, using a cardiopulmonary bypass system in cardiac surgery and other cases requiring extracorporeal circulation.

Several oxygen delivery devices are available, classified as:

Low-flow systems: The simplest method for delivering an oxygen-air mixture; for example, oxygen delivered via a flowmeter connected to a nasal cannula or face mask.
High-flow systems: Designed to meet the patient's total respiratory gas requirements, providing a constant and predetermined oxygen concentration unaffected/diluted by ambient air; e.g., Venturi masks, where, once the oxygen flow is set, the inspired air is enriched with a constant oxygen concentration.
Demand valve systems: Designed to deliver 100% oxygen without contact with ambient air. Intended for short-term use only, in emergencies.
Hyperbaric oxygen therapy: Performed in a specially designed pressurized chamber capable of maintaining pressures up to three times atmospheric pressure. Hyperbaric oxygen therapy may also be administered via a tightly sealed mask, helmet, or endotracheal tube.

Normobaric Oxygen Therapy
Normobaric oxygen therapy refers to the administration of an oxygen-enriched gas mixture (i.e., with an inspired oxygen fraction (FiO₂) exceeding 21%) at a partial pressure between 0.21 and 1 atmosphere (0.213–1.013 bar).

In patients without respiratory insufficiency, oxygen may be administered via spontaneous ventilation using nasal cannulas, nasopharyngeal catheters, or suitable masks.

In patients with respiratory insufficiency or under anaesthesia, oxygen must be administered via assisted ventilation.

Oxygen cylinders contain a maximum internal pressure of approximately 200 bar. Pressure is regulated by a reducer and displayed on the pressure gauge. Multiplying the gauge reading by the cylinder's volume (in litres) gives the amount of oxygen remaining in the cylinder.

With spontaneous ventilation
Patients with chronic respiratory insufficiency: administer oxygen at a flow rate of 0.5 to 2 litres/minute, adjustable according to blood gas analysis.
Patients with acute respiratory insufficiency: administer oxygen at a flow rate of 0.5 to 15 litres/minute, adjustable according to blood gas analysis.

With assisted ventilation
The minimum FiO₂ is 21%, up to a maximum of 100%.
The therapeutic goal of oxygen therapy is to ensure that arterial oxygen partial pressure (PaO₂) is not below 8 kPa (60 mmHg) or that arterial haemoglobin oxygen saturation is not below 90%, achieved by adjusting the inspired oxygen fraction (FiO₂).

Dosage must be adjusted according to individual patient needs.
The general recommendation is to use the lowest FiO₂ necessary to achieve the desired therapeutic effect, i.e., normal PaO₂ values. In cases of severe hypoxaemia, higher FiO₂ values (entailing potential oxygen toxicity risk) may be indicated.

Continuous therapy monitoring and ongoing assessment of therapeutic effect are required, through measurement of PaO₂ or, alternatively, arterial oxygen saturation (SpO₂).

In short-term oxygen therapy, the inspired oxygen fraction (FiO₂) should maintain PaO₂ > 8 kPa, with or without positive end-expiratory pressure (PEEP) or continuous positive airway pressure (CPAP), while avoiding FiO₂ values > 0.6 (i.e., >60% oxygen in the inhaled gas mixture) whenever possible.

For long-term treatment, the need for supplemental oxygen should be determined by arterial blood gas measurements. To avoid excessive carbon dioxide accumulation, blood oxygen levels must be monitored to adjust oxygen therapy in patients with hypercapnia.

Low oxygen concentrations should be used in patients with respiratory insufficiency whose respiratory drive depends on hypoxia (e.g., due to COPD). The oxygen concentration in inhaled air should not exceed 28%; in some patients, even 24% may be excessive.

If oxygen is mixed with other gases, its concentration in the inhaled gas mixture must be maintained at least at 21%. In practice, levels below 30% are generally avoided. When necessary, the inspired oxygen fraction may be increased up to 100%.

Neonates may receive 100% oxygen when required. However, careful monitoring during treatment is essential. It is recommended to avoid oxygen concentrations exceeding 40% to reduce the risk of lens damage or pulmonary collapse. Arterial oxygen pressure (PaO₂) should be monitored; however, if maintained below 13.3 kPa (100 mmHg) and significant oxygenation fluctuations are avoided, the risk of ocular damage is reduced. Additionally, the risk of ocular damage may be reduced by avoiding significant oxygenation fluctuations (see also section “Precautions for Use”).

Hyperbaric Oxygen Therapy
Hyperbaric oxygen therapy refers to treatment with 100% oxygen at pressures exceeding 1.4 times atmospheric pressure at sea level (1 atm = 101.3 kPa = 760 mmHg). For safety reasons, pressure in hyperbaric oxygen therapy should not exceed 3 atm.

Oxygen must be administered in a hyperbaric chamber.

Session duration in a hyperbaric chamber at pressures between 2 and 3 atmospheres (i.e., 2.026–3.039 bar) ranges from 60 minutes to 4–6 hours. These sessions may be repeated 2 to 4 times daily, depending on the patient's clinical condition.

Compression and decompression should be performed slowly according to standard procedures to avoid barotrauma to air-containing anatomical cavities communicating with the outside.

Hyperbaric oxygen therapy must be administered by qualified personnel trained in this treatment.

Overdose
In case of oxygen toxicity related to hyperoxia, oxygen therapy should be reduced or, if possible, discontinued, and symptomatic treatment initiated.

Instructions for Use and Handling
Medical oxygen cylinders, as well as fixed cryogenic containers, are intended exclusively for containing/transporting oxygen for inhalation, for therapeutic use.

Cylinders must be transported using appropriate means to protect them from impact and falling risks.

Strictly follow these instructions:

Carefully read the container’s instruction and user manual (packaging).
Ensure all equipment is in good condition.
Secure cylinders in an upright position to prevent falls; protect containers from impact and maintain them at temperatures below 50°C; ensure adequate ventilation in areas where the product is used. Cylinders must be fitted with a protective valve cap (tulip).
Handle equipment with clean hands, free from grease or oil.
Lift and move cylinders only using a suitable trolley; never lift a cylinder by its valve.
Use oxygen-specific, compatible connectors, hoses, or flexible couplings.
Pay particular attention to securing pressure reducers to cylinders, especially if not integrated into the container closure system, to prevent accidental breakage.
Absolutely avoid any intervention on container fittings, delivery equipment, or related accessories or components (OIL AND GREASE MAY SPONTANEOUSLY IGNITE IN CONTACT WITH OXYGEN).
Do not lubricate or attempt to repair a defective valve.
Absolutely avoid handling equipment or components with hands, clothing, or face contaminated with grease, oil, creams, or ointments.
Contact with frozen parts (for cryogenic containers) is strictly prohibited.

General Instructions for Use

Cylinders equipped with shut-off valve only

Remove the protective cap, if present
Ensure that the delivery valve is closed
Remove the tamper-evident seal
Connect the pressure regulator to the cylinder valve and the corresponding flowmeter
Connect the humidifier/bubbler
Connect the nasal cannula with mask or goggles to the humidifier
Slowly open the main valve until fully open
Adjust the flowmeter to the required flow rate (litres/minute)

NOTE: FOR MORE DETAILS, REFER TO THE INSTRUCTIONS FOR USE OF THE
CONTAINER
WARNING

Open container closure systems (valve or tap) gradually to avoid pressure surges.
Do not force taps or valves when opening or closing.
Never position yourself in front of the gas outlet port of the tap/valve, but always to the side. Do not expose yourself or the patient to the direct gas stream.
Do not use oil or grease in contact with the gas.
Do not completely empty the container.
After use, close the cylinder valve.
In case of gas leakage, close the valve immediately and notify the technical service of the supplier indicated in the Container’s Instructions for Use.
Use only containers suitable for the product, and appropriate for the intended operating pressure and temperature.

Disposal

Store empty cylinders with valves closed.
Do not discharge into sewers, basements, or pits where gas accumulation could be hazardous.
Return empty or unused containers, even if only partially empty, to the supplier. Any residual unused medicinal product remaining in the pressurized cylinder will be safely eliminated through appropriate procedures in a well-ventilated area by the company responsible for refilling the container.

Observe all applicable rules concerning the use and handling of pressurized cylinders and
containers holding cryogenic liquids.
Store cylinders at temperatures between -10°C and 50°C, in well-ventilated areas or in well-ventilated sheds, avoiding the formation of oxygen-enriched atmospheres (O₂ > 21% vol), in an upright position with valves closed and protected from rain and adverse weather conditions, direct sunlight, and away from heat sources, ignition sources, and combustible materials. Empty containers or those containing other types of gas must be stored separately.
Fixed cryogenic containers installed at healthcare facilities must be located outdoors.