Oxygen Voksisud: detailed information

OSP

Package leaflet: Information for the patient

OXYGEN VOXISUD 200 BAR COMPRESSED MEDICINAL GAS, CRYOGENIC MEDICINAL GAS

Oxygen
Please read this leaflet carefully before this medicine is administered to you, 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, tell your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet:

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

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

Ossigeno VOXISUD contains oxygen, a gas naturally present in the air we breathe.
The administration of medicinal oxygen is necessary to increase the amount of oxygen in all
body tissues, in conditions caused by diseases leading to respiratory disorders. Therefore, Ossigeno
VOXISUD is indicated in patients of all ages :

for the treatment of respiratory disorders (acute and chronic respiratory failure),
for anaesthesia,
in intensive care, a hospital unit where critically ill patients are admitted,
in hyperbaric chambers, a room where air pressure is higher than that in the atmosphere.

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

Normobaric oxygen therapy
Under normal conditions, there are no contraindications.
You will not be given Ossigeno VOXISUD in a hyperbaric chamber if:
you suffer from a lung disease that causes air bubbles to form in the lungs (bullous emphysema)
you suffer from asthma
you currently have or have previously had a collapsed lung (pneumothorax)
you suffer from a disease causing obstruction of the airways, making it difficult to empty air from the lungs, resulting in shortness of breath (also known as dyspnea) (COPD)
you suffer from lung inflammation (Pneumocystis carinii pneumonia)
you suffer from a condition characterized by uncontrolled body movements (epilepsy)
you are afraid 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 an optic nerve disease
you suffer from malignant tumors
you have high levels of acid in the blood (acidosis)
you are taking medications to treat tumors such as doxorubicin, adriamycin, daunorubicin, bleomycin, cis-platinum (see section Other medicines and Ossigeno VOXISUD),
you are taking medications to treat inflammation such as corticosteroids (see section Other medicines and Ossigeno VOXISUD),
you are taking a medication to treat alcohol dependence (disulfiram – see section Other medicines and Ossigeno VOXISUD),
you consume alcohol,
you have recently been exposed to toxic substances (aromatic hydrocarbons),
you smoke or use nicotine-based medications to help quit smoking
the newborn was born prematurely

Warnings and precautions
Speak to your doctor or nurse before you are given Ossigeno VOXISUD.
Inform your doctor:

if you suffer from a thyroid disease, a gland located in the neck that is overactive (hyperthyroidism)
if you suffer from vitamin C and/or vitamin E deficiency or if you have anemia caused by lack of a substance called glutathione (an antioxidant that counteracts aging)
if you have undergone treatment for paraquat poisoning (a herbicide)
if you consume alcohol (oxygen may increase respiratory depression caused by alcohol)
if you are taking medications to treat epilepsy (barbiturates) and/or pain (opioids)
if you suffer from airway inflammation making breathing difficult (Chronic Obstructive Bronchopulmonary Disease COPD)
if you suffer from specific diseases (e.g. COPD; cystic fibrosis, pathological obesity, chest wall deformities, neuromuscular disorders, respiratory depressant drug overdose), which may reduce sensitivity to carbon dioxide pressure in the blood or lead to increased carbon dioxide concentration in the blood (hypercapnic respiratory failure)
if you have had lung injury caused by the use of bleomycin. Also inform your doctor if you have recently undergone an X-ray.

Children
In premature infants and full-term newborns, oxygen therapy may cause eye damage (retinopathy of prematurity), lung damage, and brain hemorrhages. The doctor will determine the appropriate oxygen concentration to administer to the newborn for optimal treatment.
Hyperbaric oxygen therapy (HBOT)
Your doctor will evaluate whether to administer oxygen in a hyperbaric chamber in case of:

inflammation of the ears and/or nose (recurrent otitis and/or sinusitis, laryngocele, mastoid cavity, vestibular syndrome, hearing loss, or recent middle ear surgery)
heart disease (ischemic and/or congestive heart conditions)
high blood pressure and you are not taking medication to treat it (untreated arterial hypertension)
lung diseases that prevent air passage (restrictive and/or severely restrictive pulmonary diseases)
an eye disease characterized by high pressure of the fluid inside the eyes (glaucoma), retinal detachment, or an eye membrane condition, even if surgically treated
history of uncontrolled body movements (seizures), sometimes with loss of consciousness (epileptic seizures)
diabetes mellitus, as hyperbaric therapy may counteract the effect of insulin and increase your blood sugar levels (hyperglycemia)
uncontrolled high fever
severe anxiety, altered perception of reality (psychosis), fear of narrow or enclosed spaces (claustrophobia)
respiratory system disorders (poorly controlled asthma, pulmonary emphysema, chronic obstructive bronchopulmonary disease (COPD)), or recent thoracic surgery

Safety precautions during transport, storage, and use of cylinders

Avoid contact of oils and greases with cylinders: for example, do not touch cylinders with hands, clothes, or face contaminated with grease, oil, creams, or various ointments.
Do not use greasy creams or lipsticks.
Do not smoke in the area where cylinders are located, especially while oxygen is being administered to the patient.
Keep cylinders away from heat sources and open flames.
Do not use any electrical equipment that may produce sparks near the cylinders, especially while oxygen is being administered to patients.
Do not use oils or greases on fittings, taps, valves, or any material in contact with oxygen (OIL AND GREASE MAY SPONTANEOUSLY IGNITE ON CONTACT WITH OXYGEN).
Do not touch frozen parts.
Use only containers that show no visible damage or that have not been damaged or exposed to extreme temperatures.
Use only equipment suitable and compatible with the specific container model.
Never introduce oxygen into a device that might contain materials that could ignite, particularly fatty substances.
Do not use pliers or other tools to open or close the cylinder valve.
Do not alter the container's shape.
In case of leakage, immediately close the cylinder valve and, if safe to do so, move the cylinder to a safer outdoor location to allow oxygen to escape freely.
Close valves on empty cylinders.
Do not administer pressurized gas.
During transport, storage, and use of cryogenic oxygen
Liquid oxygen may cause cold burns.
If liquid oxygen comes into contact with skin or eyes, wash the area thoroughly with cold water or apply cold compresses. Seek medical attention immediately.

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

catecholamines (e.g. adrenaline, noradrenaline), medicines that produce effects on multiple body 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,
antibiotics (e.g. actinomycin, nitrofurantoin, bleomycin), 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,
vitamin K supplements (menadione), nitric oxide (another medicinal gas).

Ossigeno VOXISUD and alcohol
Do not consume alcohol during treatment with Ossigeno VOXISUD, as oxygen may worsen respiratory depression (difficulty breathing) caused by alcohol.
Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, planning a pregnancy, or breastfeeding, consult your doctor or nurse before taking this medicine.
Pregnancy
Normobaric oxygen therapy
Oxygen may be used during pregnancy only when necessary.
Hyperbaric oxygen therapy
Ossigeno VOXISUD will not be administered to you in a hyperbaric chamber during the first 3 months of pregnancy. The doctor will decide whether to administer this treatment in case of critical conditions (e.g. severe carbon monoxide poisoning).
Breastfeeding
There are no contraindications for the use of oxygen during breastfeeding.
Driving and using machines
Normobaric oxygen therapy
This medicine does not impair or impairs only negligibly the ability to drive or use machines.
Avoid driving vehicles and using machinery until any negative effects on attention and alertness have completely disappeared.
Hyperbaric oxygen therapy
Visual and hearing disturbances that may affect the ability to drive and use machinery have been reported after oxygen administration.
Avoid driving vehicles and using machinery until any negative effects on attention and alertness have completely disappeared.

3. How Oxygen VOXISUD will be administered to you

This medicine will be administered to you through inhaled air, always following exactly the instructions of your doctor or nurse. If you have any doubts, consult your doctor.
If you do not have respiratory failure, Oxygen VOXISUD is usually inhaled through the nose and mouth via a nasal cannula or a face mask.
If you suffer from respiratory failure or are undergoing anesthesia, Oxygen VOXISUD will be administered to you via assisted ventilation.
The dose will be determined by your doctor based on your health status.
During treatment with Oxygen VOXISUD, your doctor may perform measurements of blood gases (oxygen and carbon dioxide) in arterial blood and will monitor oxygen levels bound to haemoglobin, a protein that carries oxygen in the blood.
If you are given more Oxygen VOXISUD than you should
It is very unlikely that you will be given more Oxygen VOXISUD than required, as your doctor or nurse will monitor you during treatment.
Symptoms of an overdose that you may experience include:

sore throat,
cough and chest pain,
difficulty breathing (dyspnoea, hypoventilation) and bluish skin (cyanosis),
damage to bronchi and lungs,
uncoordinated movements,
tingling in limbs,
visual and hearing disturbances,
nausea, dizziness,
anxiety, confusion and irritability,
muscle cramps and spasms,
loss of consciousness,
uncontrolled body movements (convulsions), sometimes with loss of consciousness (epileptic seizures),
eye damage (retinopathy of prematurity) in premature infants,
respiratory depression and increased acid levels in the blood in patients at risk of high carbon dioxide concentration in the blood (hypercapnic respiratory failure).

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Tissues show different sensitivity to hyperoxia, with the lungs, brain, and eyes being the most sensitive.

During treatment with OXYGEN VOXISUD, the following side effects may occur, grouped by frequency:

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

Eye damage (retinopathy of prematurity)

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

Pulmonary toxicity characterized by:
- Airway infection characterized by substernal pain and dry cough (tracheobronchitis)
- Fluid accumulation in the tissues lining the lung alveoli (interstitial edema)
- Lung disease characterized by the formation of scar tissue replacing normal lung tissue (pulmonary fibrosis)
Increased carbon dioxide in the blood (hypercapnia), leading to:
- Hypoventilation
- Increased acid levels in the blood (respiratory acidosis)
- Respiratory arrest
Dryness and irritation of mucous membranes (congestion or occlusion of the paranasal sinuses with pain and bleeding), local irritation and inflammation of the mucosa

Other reported side effects:

Slight reduction in heart rate and cardiac output
Atelectasis
Lung injury
Dryness and irritation of the eyes
Slowed elimination of nasal secretions

Adverse reactions associated with hyperbaric oxygen therapy:

Very common (may affect up to 1 in 10 people)

Ear pain
Progressive myopathy
Tissue injury caused by imbalance between air pressure within a body cavity and the surrounding environmental pressure (barotrauma), which may present as ear pain and possible ear bleeding, toothache, intestinal gas release (flatulence), or colic pain

Common (may affect up to 1 in 100 people)

Uncontrollable body movements (seizures)

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

Tympanic membrane perforation

Rare (may affect up to 1 in 10,000 people)

Shortness of breath (dyspnea)
Decreased blood glucose levels (hypoglycemia) in diabetic patients

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

Respiratory disorders
Involuntary muscle contractions (muscle spasms)
Dizziness
Hearing loss
Ringing in the ears (tinnitus)
Nausea
Abnormal behaviour
Blurred vision
Reduced peripheral vision
Decreased vision due to reduced transparency of the lens (cataract)
Acute inflammation of the middle ear with serum accumulation (acute serous otitis media)

Regarding the cryogenic formulation only:

Cold burns may occur following direct contact with liquid oxygen (see section "Safety precautions").

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, tell your doctor, pharmacist, or nurse. You can also report side effects directly via the national reporting system at http://www.aifa.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 VOXISUD

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 VOXISUD Contains

The active substance is oxygen.

Description of the Appearance of Ossigeno VOXISUD and Package Contents
Compressed medicinal gas
OSSIGENO VOXISUD compressed medicinal gas is supplied in cylinder packs, in compressed gaseous form at 200 bar at 15°C. The cylinders are made of steel and equipped with valves compatible with a pressure reducer.
Cryogenic medicinal gas
OSSIGENO VOXISUD cryogenic medicinal gas is supplied in fixed cryogenic containers.
Available pack sizes:
Compressed medicinal gas
Cylinder pack containing 16 steel cylinders of 40, 50 litres.
Fixed cryogenic medicinal gas
Fixed cryogenic container of 6000, 10000 litres.
Not all pack sizes may be marketed.
Marketing Authorization Holder
VOXISUD S.r.l.
Via Arpino 24
03036 Isola del Liri (FR)
Manufacturer
Compressed medicinal gas
Voxisud srl – Via Arpino, 6 – 03036 Isola del Liri (FR)
Cryogenic medicinal gas (fixed containers)
Voxisud srl – Via Arpino, 6 – 03036 Isola del Liri (FR)
___________________________________________________________________________________
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 mm Hg) should be administered.
Higher concentrations should be administered for the shortest possible duration, with frequent close monitoring of blood gas analysis.
Oxygen can be safely administered at the following concentrations and for the following durations:
Up to 100% for less than 6 hours
60–70% for 24 hours
40–50% during the second 24-hour period.
Oxygen may become potentially toxic after two days at concentrations exceeding 40%.
Low oxygen concentrations should be used in patients with respiratory insufficiency in whom the respiratory drive is hypoxia-dependent. In these cases, treatment must be closely monitored by measuring arterial oxygen tension (PaO₂), or via pulse oximetry (arterial oxygen saturation – SpO₂), along with clinical assessment.
Administering oxygen to patients with respiratory insufficiency caused by drugs (opioids, barbiturates) or chronic obstructive pulmonary disease (COPD) may further worsen respiratory failure due to hypercapnia resulting from elevated blood carbon dioxide levels, which suppresses respiratory drive. High oxygen concentrations in the inhaled air or gas mixture lead to a decrease in nitrogen concentration and partial pressure. This 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 can 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
Particular 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 (see section 4.8). 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 and lung injury, even when administered several 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 4.5).
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 4.8), 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 oxygenation are not precisely defined. If supplemental oxygen is required, it should be carefully monitored and guided by pulse oximetry.
In both term and preterm neonates, administration of oxygen at concentrations exceeding 30–40% may cause adverse effects such as retrolental fibroplasia, chronic lung disease, and intraventricular haemorrhage. This is due to insufficient production of endogenous antioxidant enzymes, resulting in an inability to counteract the production and toxic effects of reactive oxygen species. In these cases, the lowest effective oxygen concentration should be administered, and arterial oxygen pressure should be closely monitored and maintained below 13.3 kPa (100 mmHg).
Hyperbaric Oxygen Therapy (HBOT)
Administration of oxygen in a hyperbaric chamber must be carefully evaluated based on the risk/benefit ratio in the following conditions:

Recurrent otitis and/or sinusitis, laryngocele, mastoid cavity, vestibular syndrome, hearing loss, or 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 carbon monoxide poisoning), hyperbaric treatment must be conducted cautiously due to potential hyperoxic vasoconstriction in the coronary circulation
Untreated pharmacological arterial hypertension
Severe restrictive and/or highly restrictive pulmonary diseases
Glaucoma, retinal detachment (even if surgically treated) (compensation maneuvers)
History of seizures, 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 the decompression phase of hyperbaric therapy, the benefit/risk ratio of hyperbaric therapy must be carefully evaluated in patients with poorly controlled asthma, pulmonary emphysema, chronic obstructive bronchopulmonary disease (COPD), or recent thoracic surgery.
Special Warnings

In oxygen-enriched environments, oxygen may saturate clothing.
It is strictly forbidden to touch frozen parts (for cryogenic containers).
Cylinders and mobile cryogenic containers must not be used if visible damage is present, if damage is suspected, or if they have been exposed to extreme temperatures.
Only equipment suitable for the specific container model and gas type may be used.
Pliers or other tools must not be used to open or close the cylinder valve to prevent damage.
The container's shape must not be altered.
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 vent safely.
Valves of empty cylinders must be closed.
Oxygen has a strong oxidizing effect and may react violently with organic substances. Therefore, special precautions are required during handling and storage of containers.
It is not permitted to release pressurized gas.

For the cryogenic formulation
Cold Burns from Direct Contact with Liquid Oxygen
Oxygen becomes liquid at approximately -183°C. At such low temperatures, direct contact of liquid oxygen with skin or mucous membranes may cause cold burns. Special safety precautions must be taken when handling cryogenic containers: appropriate protective clothing (gloves, goggles, loose clothing, and pants covering shoes) must be worn. If liquid oxygen contacts skin or eyes, the affected areas must be rinsed with abundant cold water or cold compresses applied, and immediate medical assistance must be sought.
Dosage, Method, and Duration of Administration
Oxygen (compressed or cryogenic) is administered via inhaled air, preferably using dedicated devices (e.g., nasal cannula or face mask); dosage is delivered independently of the medicinal gas packaging via dosing devices (flowmeters).
With these systems, oxygen is delivered through the inspired air, while exhaled gas and any excess oxygen exit the patient's inspiratory circuit, mixing 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 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 an internal pressure of approximately 150–200 bar. This high pressure is regulated by a pressure reducer, and the pressure can be read on the manometer. Multiplying the manometer reading by the cylinder's volume in litres gives the remaining oxygen volume available in the cylinder.
(Example: Content calculation: a cylinder has a volume of 10 litres and the manometer reads 200 bar, resulting in 2000 litres of oxygen; at a consumption rate of 2 litres per minute, the cylinder will be empty after approximately 16 hours).
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.
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.
The duration of sessions 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 risk to air-containing anatomical cavities communicating with the external environment.
Hyperbaric oxygen therapy must be performed by qualified personnel trained in this treatment.
Instructions for Use and Handling
Medicinal oxygen cylinders and 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 fall risks.
Strictly follow these instructions:

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

Instructions for Use
Cylinders equipped with a simple shut-off valve only

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 fully
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 fully
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)

WARNING

Open container closure systems (valve or tap) gradually to avoid pressure surges.
Do not force taps or valves when opening or closing.
Never stand directly in front of the gas outlet of the tap/valve; always stand to the 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 notify the technical service of the supplier indicated in the container's user manual.
Use only containers suitable for the product and intended pressure and temperature conditions.

During Use

Do not use greasy creams or lipsticks.
Do not smoke.
Do not bring open flames near the container.
No electrical equipment capable of producing sparks should be used 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 may contain combustible materials, especially greasy substances.

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 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 same container.

Patient information leaflet

OXYGEN VOXISUD 200 BAR COMPRESSED MEDICINAL GAS, CRYOGENIC MEDICINAL GAS

Oxygen
Please read this leaflet carefully before using this medicinal product as 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 medicinal product has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, as it may be harmful.
If you experience any adverse reaction, including those not listed in this leaflet, consult your doctor or pharmacist. See section 4.

Contents of this leaflet:

What OXYGEN VOXISUD is and what it is used for
What you need to know before using OXYGEN VOXISUD
How to use OXYGEN VOXISUD
Possible side effects
How to store OXYGEN VOXISUD
Contents of the pack and other information

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

Ossigeno VOXISUD contains oxygen, a gas naturally present in the air we breathe.
The administration of medical oxygen is necessary to increase the amount of oxygen in all
tissues of the body, in the presence of diseases causing respiratory disorders. Therefore,
Ossigeno VOXISUD is indicated in patients of all ages:

for the treatment of respiratory disorders (acute and chronic respiratory failure).

2. What you need to know before using Ossigeno VOXISUD

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

if you have a thyroid disease, a gland in the neck that is overactive (hyperthyroidism)
if you have a deficiency of vitamin C and/or vitamin E or if you have anemia caused by a deficiency of a substance called glutathione (an antioxidant that counteracts aging)
if you have undergone treatment for paraquat poisoning (a herbicide)
if you consume alcohol (oxygen may increase respiratory depression caused by alcohol)
if you are taking medicines to treat epilepsy (barbiturates) and/or pain (opioids)
if you suffer from airway inflammation that makes breathing difficult (Chronic Obstructive Pulmonary Disease, COPD)
if you have certain conditions (e.g. COPD; cystic fibrosis, pathological obesity, chest wall deformities, neuromuscular disorders, drug overdose causing respiratory depression), which may reduce sensitivity to carbon dioxide blood pressure

or lead to an increase in carbon dioxide concentration in the blood (hypercapnic respiratory failure)
OK for variations N1B/2018/371 + N1B/2015/5637

if you have previously experienced lung injury due to bleomycin use
Additionally, inform your doctor if:
you have recently undergone an X-ray examination.

Children
In premature infants and full-term newborns, oxygen therapy may cause eye damage (retinopathy of prematurity). The doctor will determine the appropriate oxygen concentration to administer to the newborn for optimal treatment.
Safety precautions
During transport, storage and use of gas cylinders

Avoid contact of oils and greases with cylinders: for example, do not touch cylinders with hands, clothing or face contaminated with grease, oil, creams or ointments.
Do not use greasy creams or lipsticks.
Do not smoke in areas where cylinders are present, especially while oxygen is being administered to the patient.
Keep cylinders away from heat sources and open flames.
Do not use any electrical equipment that may produce sparks near the cylinders, especially while oxygen is being administered to patients.
Do not use oils or greases on connectors, taps, valves or any material in contact with oxygen (OIL AND GREASE MAY SPONTANEOUSLY IGNITE ON CONTACT WITH OXYGEN).
Use only containers that show no visible damage or that have not been damaged or exposed to extreme temperatures.
Use only equipment suitable and compatible with the specific container model.
Never introduce oxygen into a device that might contain materials capable of catching fire, particularly fatty substances.
Do not use pliers or other tools to open or close the cylinder valve.
Do not alter the shape of the container.
In case of leakage, immediately close the cylinder valve and, if safe to do so, move the cylinder to a safer outdoor location to allow oxygen to escape freely.
Close valves on empty cylinders.
During transport, storage and use of cryogenic oxygen
Liquid oxygen may cause cold burns. If liquid oxygen comes into contact with the skin or eyes, wash the affected area with abundant cold water or apply cold compresses. Seek immediate medical advice.

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

catecholamines (e.g. adrenaline, noradrenaline), medicines that affect multiple body organs and are generally used in 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,
antibiotics (e.g. bleomycin, actinomycin, nitrofurantoin), medicines used to treat infections,
vitamin K supplements (menadione),
medicines for mental disorders (e.g. promazine, chlorpromazine, thioridazine),
chloroquine, a medicine used to treat malaria,
nitric oxide, another medicinal gas.
Ossigeno VOXISUD and alcohol
Do not consume alcohol during treatment with Ossigeno VOXISUD, as oxygen may worsen respiratory depression (difficulty breathing) caused by alcohol.

Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, planning to become pregnant, or breastfeeding, ask your doctor or pharmacist for advice before taking this medicine.
Use Ossigeno VOXISUD during pregnancy only if strictly necessary.
Ossigeno VOXISUD may be used during breastfeeding.
Driving and use of machinery
This medicine does not impair or impairs negligibly the ability to drive vehicles or operate machinery.
Avoid driving vehicles and operating machinery until any adverse effects on attention and alertness have completely disappeared.

3. How to use Ossigeno VOXISUD

Use this medicine exactly as instructed by your doctor or pharmacist. If you have
any doubts, consult your doctor.
If you do not have respiratory insufficiency, Ossigeno VOXISUD is usually inhaled through the nose and
mouth via a nasal cannula or a face mask.
If you suffer from respiratory insufficiency or are undergoing anaesthesia, Ossigeno VOXISUD will be
administered via assisted ventilation.
The dose will be determined by your doctor based on your health status.
During treatment with Ossigeno VOXISUD, your doctor may monitor oxygen levels in your body.
If you use more Ossigeno VOXISUD than you should
If you use more Ossigeno VOXISUD than recommended, contact your doctor or go to hospital
immediately.
Symptoms of an overdose that you may experience include:

sore throat,
cough and chest pain,
difficulty breathing (dyspnoea, hypoventilation) with bluish skin (cyanosis),
damage to bronchi and lungs,
uncoordinated movements,
tingling in limbs, muscle cramps and spasms,
disturbances of vision and hearing,
nausea, dizziness,
anxiety and confusion,
loss of consciousness,
uncontrolled body movements (seizures), sometimes with loss of consciousness (epileptic attacks).

Treatment
If you have taken an excessive dose, your doctor will provide appropriate treatment and monitor you closely.
In most cases, symptoms resolve within 4 hours after stopping the treatment.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone experiences them.
The following adverse reactions may occur during treatment with Ossigeno VOXISUD:

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

Eye damage (retinopathy of prematurity)

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

Pulmonary toxicity characterized by:
airway infection characterized by pain behind the breastbone and dry cough (tracheobronchitis)
accumulation of fluid occurring in the tissues lining the lung alveoli (interstitial edema)
respiratory disease characterized by the formation of scar tissue replacing normal lung tissue (pulmonary fibrosis)
Increased carbon dioxide in the blood (hypercapnia), leading to:
hypoventilation
increased acid levels in the blood (respiratory acidosis)
respiratory arrest
Dryness and irritation of mucous membranes (congestion or obstruction of the paranasal sinuses with pain and bleeding)
Local irritation and inflammation of the mucosa

Other reported adverse reactions:

Slight reduction in heart rate and cardiac output.
Atelectasis
Lung injuries
Dryness and irritation of the eyes
Slowed clearance of nasal secretions

Reporting of adverse reactions
If you experience any adverse reaction, including those not listed in this leaflet, please contact your doctor, pharmacist, or nurse. You can also report adverse reactions directly through the national reporting system at http://www.aifa.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 VOXISUD

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 via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package Contents and Other Information

What Ossigeno VOXISUD Contains

The active substance is oxygen.

Description of the Appearance of Ossigeno VOXISUD and Contents of the Package
Compressed medicinal gas
OSSIGENO VOXISUD compressed medicinal gas is supplied in cylinders in compressed gaseous form at 200 bar at 15°C. The cylinders are made of steel and equipped with valves compatible with pressure regulators or integrated pressure-reducing valves.
Cryogenic medicinal gas
OSSIGENO VOXISUD cryogenic medicinal gas is supplied in mobile cryogenic containers.
Available pack sizes:
Compressed medicinal gas
Steel cylinders of 0.5, 1, 2, 5, 7, 10, 14, 27, 40, 50 litres.
Cryogenic medicinal gas
Mobile cryogenic containers of 31, 41 litres.
Not all pack sizes may be marketed.

Marketing Authorization Holder
VOXISUD S.r.l.
Via Arpino 24
03036 Isola del Liri (FR)

Manufacturer
Compressed medicinal gas and Cryogenic medicinal gas (mobile containers)
VOXISUD S.r.l. - Via Arpino 24, 03036 Isola del Liri (FR)

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 administered for the shortest possible duration, with frequent close monitoring of blood gas analysis.
Oxygen can be safely administered at the following concentrations and for the following durations:
Up to 100% for less than 6 hours
60–70% for 24 hours
40–50% during the second 24-hour period.
Oxygen may become toxic after two days when administered at concentrations exceeding 40%.
Low oxygen concentrations should be used in patients with respiratory failure whose respiratory drive depends on hypoxia. In these cases, treatment must be closely monitored by measuring arterial oxygen tension (PaO₂), or via pulse oximetry (arterial oxygen saturation – SpO₂) and clinical assessment.
Administering oxygen to patients with drug-induced respiratory failure (e.g., opioids, barbiturates) or chronic obstructive bronchopulmonary disease (COPD) may further worsen respiratory failure due to hypercapnia caused by elevated carbon dioxide levels in the blood, which suppresses respiratory drive.
High oxygen concentrations in the inhaled air or gas mixture lead to a decrease in nitrogen concentration and partial pressure. This 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 can impair arterial blood oxygenation, as gas exchange is prevented 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 those 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). Supplemental oxygen administration may cause respiratory depression and increased PaCO₂, leading to symptomatic respiratory acidosis (see section 4.8). 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 damage, even years after the initial lung injury caused by bleomycin. The target oxygen saturation in these patients may need to be lower than in others (see section 4.5).

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 4.8), 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 oxygenation are not precisely defined. If supplemental oxygen is required, it should be carefully monitored and guided by pulse oximetry.
In both term and preterm neonates, administering oxygen at concentrations above 30–40% may cause adverse effects such as retrolental fibroplasia, chronic lung disease, and intraventricular haemorrhage. This is due to insufficient production of endogenous antioxidant enzymes, resulting in an inability to counteract the production and toxic effects of reactive oxygen species. In these cases, the lowest effective oxygen concentration should be administered, and arterial oxygen pressure should be closely monitored and maintained below 13.3 kPa (100 mmHg).

Special Warnings

In hyperoxic environments, oxygen may saturate clothing.
It is strictly forbidden to touch frozen parts (for cryogenic containers).
Cylinders and mobile cryogenic containers must not be used if there are visible damages, suspected damage, or exposure to extreme temperatures.
Only equipment suitable for the specific container model and gas type may be used.
Pliers or other tools must not be used to open or close cylinder valves to prevent damage.
The container's shape must not be altered.
In case of leakage, the cylinder valve must be closed immediately, if safely possible. If the valve cannot be closed, the cylinder must be moved to a safe outdoor location to allow oxygen to escape safely.
Valves on empty cylinders must be closed.
Oxygen is a strong oxidizing agent and may react violently with organic substances. Therefore, special precautions are required for handling and storage of containers.
It is not permitted to release pressurized gas.

For cryogenic formulation:
Cold burns from direct contact with liquid oxygen
Oxygen becomes liquid at approximately -183°C. At such low temperatures, direct contact of liquid oxygen with skin or mucous membranes may cause cold burns. Special safety precautions must be taken when handling cryogenic containers: appropriate protective clothing (gloves, goggles, loose clothing, and pants covering shoes) must be worn. If liquid oxygen comes into contact with skin or eyes, the affected areas must be washed immediately with abundant cold water or cold compresses applied, and immediate medical assistance must be sought.

Dosage, Method, and Duration of Administration
Oxygen (compressed or cryogenic) is administered via inhaled air, preferably using dedicated devices (e.g., nasal cannula or face mask). Dosage is delivered independently of the medicinal gas packaging via dosing devices (flowmeters).
With these systems, oxygen is delivered through the inspired air, while expired gas and any excess oxygen leave 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 can be administered via spontaneous ventilation using nasal cannulas, nasopharyngeal catheters, or suitable masks.
In patients with respiratory failure or under anesthesia, oxygen must be administered via assisted ventilation.
Oxygen cylinders contain an internal pressure of approximately 150–200 bar. This high pressure is regulated by a pressure reducer, and the pressure is displayed on the manometer. Multiplying the manometer reading by the cylinder's volume in litres gives the amount of oxygen remaining in the cylinder.
(Example: Content calculation: a cylinder has a volume of 10 litres and the manometer reads 200 bar, resulting in 2000 litres of oxygen available: at a consumption rate of 2 litres per minute, the cylinder will be empty after approximately 16 hours.)

With spontaneous ventilation
Patients with chronic respiratory failure: administer oxygen at a flow rate between 0.5 and 2 litres/minute, adjustable based on blood gas analysis.
Patients with acute respiratory failure: administer oxygen at a flow rate between 0.5 and 15 litres/minute, adjustable based on blood gas analysis.

Instructions for Use and Handling
Medicinal oxygen cylinders and 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 falls.
Strictly follow the instructions below:

Carefully read the instruction and user manual of the container (packaging).
Ensure all equipment is in good condition.
Securely fasten cylinders and base units to keep them in an upright position and prevent accidental falls. Protect containers from impacts and maintain them at temperatures below 50°C. Ensure adequate ventilation in rooms where the product is used. Cylinders must be fitted with a protective cap/tulip over 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 only oxygen-specific connectors, connecting tubes, or flexible hoses.
Special attention must be paid to securing pressure reducers to cylinders, if not already integrated into the container closure system, to avoid accidental breakage.
It is strictly forbidden to modify any container fittings, delivery equipment, or their accessories or components (OIL AND GREASE MAY IGNITE ON CONTACT WITH OXYGEN).
Do not lubricate or attempt to repair a defective valve.
It is strictly forbidden to handle equipment or components with hands, clothing, or face contaminated with grease, oil, creams, or ointments.
It is strictly forbidden to touch frozen parts (for cryogenic containers).

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 fully
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 fully
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)

WARNING

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; always stand to the 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 notify the technical service of the supplier indicated in the container's user manual.
Use only containers suitable for the product and compatible with the required operating pressure and temperature.

During Use

Do not use greasy creams or lipsticks.
Do not smoke.
Do not bring open flames near the container.
No electrical equipment that may produce sparks should be used 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 may contain combustible materials, especially greasy substances.

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 through appropriate procedures in a well-ventilated area by the company responsible for refilling the container.