Entonox

Patient Information Leaflet

ENTONOX, 50% + 50%, compressed medical gas
Dinitrogenii oxidum + Oxygenium
Please read this leaflet carefully before using this medicine, as it contains important information for you.

• Keep this leaflet so that you can read it again if necessary.
• If you have any questions, please consult your doctor or nurse.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. The medicine may harm someone else, even if their symptoms are the same.
• If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor or nurse. See section 4.

Table of contents:

1. What ENTONOX is and what it is used for
2. Important information before using ENTONOX
3. How to use ENTONOX
4. Possible side effects
5. How to store ENTONOX
6. Contents of the pack and other information

1. What ENTONOX is and what it is used for

ENTONOX contains a ready-to-use mixture of nitrous oxide (medical "laughing gas", N₂O) and oxygen (medical oxygen, O₂), each at 50%, and is administered by inhalation.

Action of ENTONOX
Nitrous oxide constitutes 50% of the gas mixture. Nitrous oxide has analgesic properties, reduces the perception of pain, and raises the pain threshold. It also has muscle-relaxing and mild sedative effects. These effects are caused by nitrous oxide acting on neurotransmitter substances in the nervous system.

The 50% oxygen concentration, approximately twice that in ambient air, ensures a safe oxygen content in the inhaled gas.

What ENTONOX is used for
ENTONOX should be used when a rapid onset and offset of analgesic effect is required, and when the pain to be treated is of mild to moderate intensity and of limited duration. ENTONOX provides analgesia within a few breaths. This effect wears off within a few minutes after discontinuation. ENTONOX can be used in adults and children aged 1 month and older.

2. Important information before using ENTONOX

When not to use ENTONOX:
Before using ENTONOX, inform the doctor if any of the following conditions are present:

• Gas-filled spaces or gas bubbles: if, due to illness or any other reason, air is suspected to be present in the pleural cavities outside the lungs, or gas bubbles are present in any organ or in the bloodstream (e.g. if the patient has been diving with scuba equipment, gas bubbles may be present in the blood), or if gas has been injected into the eye (e.g. due to retinal detachment or similar conditions). Such air bubbles may expand and thereby cause organ damage.
• Heart diseases: If the patient has circulatory failure or significantly impaired heart function, the slight relaxing effect of nitrous oxide on the heart muscle may further worsen cardiac function.
• Central nervous system injury: if intracranial pressure is elevated, for example due to brain tumor or intracerebral hemorrhage, because nitrous oxide may further increase pressure within the brain and potentially cause damage.
• Vitamin deficiency: if vitamin B12 or folic acid deficiency has been diagnosed and is untreated, administration of nitrous oxide may exacerbate symptoms caused by vitamin B12 and folic acid deficiency.
• Intestinal obstruction: if severe abdominal pain is present, a symptom which may indicate intestinal obstruction, ENTONOX may worsen intestinal distension.
• Facial or jaw injuries, where use of a face mask may cause difficulties or risk.

Warnings and precautions
Please also inform the doctor about the following symptoms/conditions:

• Reduced level of consciousness or persistent confusion: Inform the doctor if symptoms of malaise or incomplete arousal due to injury or illness are present. This information is important because the calming effect of nitrous oxide in ENTONOX may enhance sedative effects, potentially impairing natural protective reflexes.
• Ear problems: such as ear infection, because ENTONOX may increase pressure in the middle ear.
• History of substance/medication abuse, because the risk of dependence on nitrous oxide is higher with repeated use. The doctor will decide whether ENTONOX can be used in such cases.
• Vitamin deficiency: If vitamin B12 or folic acid deficiency is suspected, nitrous oxide may worsen symptoms caused by deficiency of vitamin B12 and folic acid.

The doctor will decide whether ENTONOX can be used.
Repeated or prolonged use of nitrous oxide may increase the risk of vitamin B12 deficiency, which may lead to bone marrow or nervous system damage. The doctor may recommend blood tests before and after administration to assess potential consequences of vitamin B12 deficiency.

ENTONOX and other medicines
Inform the doctor or nurse about all medicines currently or recently taken, as well as any medicines the patient plans to take.

• Methotrexate, used in the treatment of, for example, rheumatoid arthritis. Taking ENTONOX with methotrexate may affect blood cell counts.
• Other medicines affecting the brain or its functions, such as benzodiazepines (sedatives) and morphine-like drugs—inform the doctor. ENTONOX may enhance the effects of these medicines. Using ENTONOX in combination with other central nervous system depressants increases the risk of adverse effects.
• Bleomycin (used in cancer treatment) or amiodarone (for treatment of cardiac arrhythmia) before taking ENTONOX, because high oxygen concentration may cause lung toxicity.
• Nitrofurantoin or antibiotics with similar action (used to treat infections)

ENTONOX intensifies adverse effects of these medicines.

Pregnancy, breastfeeding, and effects on fertility
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a child, she should consult a doctor or nurse before taking this medicine.
ENTONOX may be used during pregnancy if the doctor considers it clinically indicated. It may also be used during childbirth. When administered close to delivery, the newborn should be monitored for breathing difficulties (respiratory depression) and other adverse effects.
ENTONOX may be used during breastfeeding, but should not be administered at the exact moment of breastfeeding.

Driving and operating machinery
Be aware that after taking ENTONOX, rest is required. Nitrous oxide, the active component of ENTONOX, is rapidly eliminated from the body after short-term inhalation. Effects on cognitive abilities may persist for several hours. For safety reasons, driving, operating machinery, and performing complex tasks should be avoided until full capacity is restored (at least 30 minutes).
Consult a healthcare professional to determine whether it is safe for the patient to drive.

3. How to use ENTONOX

ENTONOX is always administered by trained personnel familiar with this medicinal product. During administration, both the patient and the delivery of ENTONOX must be monitored to ensure safe use. After administration has ended, the patient will remain under the supervision of competent medical staff until full consciousness is regained.
ENTONOX must always be used according to the instructions of a doctor or nurse. If in doubt, consult a doctor or nurse. The doctor or nurse should explain to the patient how ENTONOX is used, how it works, and what its effects are.
Usually, ENTONOX is inhaled through a face mask connected to a special valve, allowing the patient to fully control the gas flow with their own breathing. The valve opens only during inhalation. ENTONOX may also be administered via a so-called nasal mask.
Regardless of which type of mask is used, breathing should be normal and regular through the mask.
Use in children
In children unable to understand or follow instructions, ENTONOX may be administered under the supervision of competent medical personnel, who may assist in holding the mask properly in place and actively monitor administration. In such cases, ENTONOX may be delivered at a constant gas flow.
After stopping ENTONOX, rest is required until full consciousness is regained.
Precautions

• Smoking or the use of open flames is strictly prohibited in rooms where ENTONOX treatment is being administered.
• ENTONOX is intended exclusively for medical purposes.

See also instructions for storage and use of cylinders (5. How to store ENTONOX)
Use of a higher than recommended dose of ENTONOX
It is highly unlikely that a patient would receive too much gas, as the patient controls the gas delivery and the gas mixture is fixed (containing 50% nitrous oxide and 50% oxygen).
If the patient breathes faster than normal and thereby inhales more nitrous oxide, they may feel noticeably drowsy and experience a certain degree of disorientation. In such a case, medical personnel must be informed immediately and administration should be stopped.
If in doubt about the use of the medicine, consult a doctor or nurse.

4. Possible adverse effects

Like all medicinal products, this medicine can cause adverse effects, although not everyone experiences them.
Common (may occur in 1 out of 10 patients):
Dizziness, feeling of disorientation (lightheadedness), euphoria, nausea and vomiting
Rare (may occur in 1 out of 100 patients):
Severe fatigue.
Feeling of pressure in the middle ear when ENTONOX is used for prolonged periods, because
ENTONOX increases pressure in the middle ear.
Sensation of bloating in the abdomen, because ENTONOX slowly increases the volume of gas in the intestines.
Frequency unknown: (cannot be estimated from available data)
Effects on nerve function, sensations of numbness and weakness, usually in the legs.
Effects on bone marrow leading to anaemia (reduced number of red blood cells) and
leukopenia (reduced number of white blood cells).
Headache and confusion may also occur after discontinuation of the medicine.
Psychiatric symptoms such as psychosis, confusion, anxiety have been reported very rarely.
Respiratory depression (inhibition of breathing function).
Dependence.
Generalized seizures.
Reporting of adverse effects
If any adverse effects occur, including any not listed in this leaflet, inform your doctor or nurse. Adverse effects can be reported directly to:
Department of Monitoring of Adverse Drug Reactions, Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
al. Jerozolimskie 181C
02-222 Warsaw
Tel.: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Adverse effects can also be reported to the marketing authorization holder.
Reporting adverse effects helps to provide more information on the safety of the medicine.

5. How to store ENTONOX
Keep the medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the label.
Do not store at temperatures below -5°C.
If there is suspicion that ENTONOX has been stored at too low a temperature, cylinders should be stored horizontally at a temperature above +10°C for at least 48 hours before use.
Contact with flammable materials may cause fire.
Vapours may cause drowsiness and dizziness.
Store away from flammable materials.
Use only in well-ventilated areas.
Do not smoke. Do not expose to high temperatures.
If there is a risk of fire – move to a safe place.
Keep the cylinder clean and dry; do not use oils or greases.
Store cylinders in a closed room designated for medical gases.
Ensure the cylinder cannot be tipped over or dropped.
Store and transport with valves closed.
Vapours may cause drowsiness and dizziness.

6. Contents of the package and other information

What ENTONOX contains

• The active substances in this medicine are: nitrous oxide 50% (medical "laughing gas"; chemical formula: N\ O) and oxygen 50% (medical oxygen; chemical formula: O\ )
• ENTONOX does not contain any other ingredients.

What ENTONOX looks like and contents of the pack
ENTONOX is a colourless, odourless gas with no taste, supplied in gas cylinders equipped with valves to control gas flow.
Pharmaceutical form: compressed medical gas
Gas cylinder shoulders are marked with white-blue stripes (oxygen/nitrous oxide). The cylinder body is white (medical gas).
Cylinder size in litres: 2 5 10
Not all pack sizes may be marketed.

Marketing Authorisation Holder:
Marketing Authorisation Holder
Linde Sverige AB
Rättarvägen 3
16968 Solna
Sweden

Manufacturer
Linde Gas AB
Baltzar von Platens gata 4-6
SE-749 47 Enköping
Sweden
Linde France
16 avenue de la Saudrune
Zone industrielle du Bois Vert
31 120 Portet sur Garonne
France
Linde Gaz Polska Sp. z o.o.
ul. Żwirowa 4
33-100 Tarnów
Poland
LINDE GAZ POLSKA Sp. z o.o.
Warsaw Branch
ul. Kasprowicza 132
01-949 Warsaw
Poland

This medicinal product is authorised in the European Economic Area member states under the following trade names:
Austria LIVOPAN
Belgium RELIVOPAN
Czech Republic ENTONOX
Cyprus ENTONOX
Denmark LIVOPAN
Finland LIVOPAN
Germany LIVOPAN
Greece ENTONOX
Hungary LIVOPAN
Iceland LIVOPAN
Italy LIVOPAN
Luxembourg RELIVOPAN
Netherlands RELIVOPAN
Norway LIVOPAN
Poland ENTONOX
Portugal LIVOPAN
Spain ENTONOX
Romania ENTONOX
Slovakia ENTONOX
Sweden LIVOPAN

February 2022

Other sources of information
Detailed information about this medicine is available on the website of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products: http://www.urpl.gov.pl

Information intended exclusively for healthcare professionals:

Safety precautions
No adverse effects have been observed in fetuses of women occupationally exposed to chronic
inhalation of nitrous oxide during pregnancy, provided an appropriate exhaust or ventilation system is installed.
Please refer to the Product Characteristics Leaflet for further information.
Special precautions must be observed when working with nitrous oxide. Nitrous oxide should be administered in accordance with local guidelines.
ENTONOX should only be used in well-ventilated areas equipped with special equipment for removing excess gas. By using an exhaust system and ensuring adequate ventilation, high concentrations of "laughing gas" in ambient air can be avoided.
High concentrations of "laughing gas" in ambient air may have a negative impact on the health of healthcare personnel or other individuals in the immediate vicinity. In various countries, local guidelines exist regarding permissible concentrations of laughing gas, known as "occupational exposure limits", often expressed as MAC (Maximum Allowable Concentration (at the workplace)), representing the time-weighted average over a working day, and MAC-C (Maximum Allowable Short-Term Concentration (at the workplace)), representing the average value during brief exposure.
To ensure that personnel are not at risk, these values must not be exceeded.
Repeated administration or exposure to nitrous oxide may lead to dependence. Caution should be exercised with healthcare personnel who are occupationally exposed to nitrous oxide.

• The valve should be opened slowly and carefully.
• The device must be switched off in case of fire or when not in use.
• During use, the cylinder must be secured in an appropriate holder.
• Consider replacing the gas cylinder when the pressure drops and the gauge indicator enters the yellow zone.
• When only a small amount of gas remains in the cylinder, the cylinder valve must be closed. It is important to leave a small residual pressure in the cylinder to prevent contamination from entering.
• After use, the cylinder valve must be manually closed tightly ("fully closed"). Pressure must be released from the regulator and connector.