Leaflet: information for the user

Actynox 50%/50% medicinal compressed gas

Nitrous oxide/oxygen

Read this leaflet carefully before starting to use this medicine, as it contains important information for you.

• Keep this leaflet, as 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, and you must not give it to others even if they have the same symptoms as you, as it may harm them.
• If you experience any side effects, consult your doctor or pharmacist, even if they are not listed in this leaflet. See section 4.

1. What is Actynox and how it is used

2. What you need to know before starting to use Actynox

3. How to use Actynox

4. Possible side effects

5. Storage of Actynox

6. Contents of the pack and additional information

Actynox contains a prepared mixture of nitrous oxide (N2O) and oxygen (O2), 50% of each, and must be used by breathing the gas mixture.

Actynox may be used in adults and children over 1 month old. The safety and efficacy of Actynox have not been established in children under 1 month old.

Effects of Actynox

Nitrous oxide constitutes 50% of the gas mixture. Nitrous oxide has an analgesic effect, reduces the sensation of pain, and elevates the pain threshold. Nitrous oxide also has a relaxing and mildly calming effect. These effects occur due to the action of nitrous oxide on substances that send signals in your nervous system.

The effect of Actynox is less in children under three years old.

The 50% oxygen concentration, roughly double that found in ambient air, ensures a safe oxygen content in the inspired gas.

What is Actynox and what is it used for

Actynox should be used when rapid onset and resolution analgesic effects are desired for pain of mild to moderate intensity and limited duration. Actynox produces analgesic effects after a few inhalations, and analgesic effects subside within minutes after stopping use.

No use Actynox:

Before using Actynox, inform your doctor if you have any of the following signs/symptoms:

• Gas-filled cavities or gas bubbles:If as a result of a disease, or for any other reason, there may be suspected air in the chest outside the lungs, or gas bubbles in the blood, or in any other organ. For example, if you have dived with scuba gear and may have gas bubbles in the blood, or if you have been treated with a gas injection in the eye, for example, for a retinal detachment or similar. These gas bubbles may expand and, therefore, cause damage.
• Heart disease:If you have heart failure or severe deterioration of heart function, since the mild relaxing effect of nitrous oxide on the heart muscle may further impair heart function.
• Central nervous system injury:If you have increased intracranial pressure, for example, as a result of a tumor or cerebral hemorrhage, since nitrous oxide may increase intracranial pressure with a possible risk of damage.
• Vitamin deficiency:If you have beendiagnosedwith a vitamin B12deficiency or a folate deficiency, but have not received treatment for it, since the use of nitrous oxide may worsen the symptoms caused by vitamin B12and folate deficiency.
• Intestinal obstruction:If you have severe abdominal discomfort: symptoms that may indicate intestinal obstruction, then Actynox may further increase intestinal dilation.

Warnings and precautions

Consult your doctor or pharmacist before using Actynox:

If you need to use Actynox for more than 6 hours consecutively, the healthcare professional will perform routine blood tests to ensure that Actynox has not affected your blood count or the way your body uses vitamin B12.

Also inform your doctor if you have any of the following signs/symptoms:

• Ear discomfort:for example, ear inflammation, since Actynox may increase middle ear pressure.
• Vitamin deficiency:ifsuspectthat you have a vitamin B12deficiency or a folate deficiency, since the use of nitrous oxide may worsen the symptoms caused by vitamin B12and folate deficiency.
• The success rate is lower in children under 3 years.

Your doctor will decide if Actynox is suitable for use.

Use of Actynox with other medications

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

If you are taking other medications that affect the brain or cerebral function, for example, benzodiazepines (tranquilizers) or similar medications to morphine, you must inform your doctor. Actynox may increase the effects of these medications. Actynox in combination with other sedatives, or other medications that affect the central nervous system, increases the risk of adverse effects.

You must also inform your doctor if you are taking medications that contain methotrexate (e.g., for rheumatoid arthritis), bleomycin (to treat cancer), furadantin or similar antibiotics (to treat infections), or amiodarone (to treat heart disease). Actynox increases the adverse effects of these medications.

Pregnancy, breastfeeding, and fertility

Actynox may be used during pregnancy in cases where it is clinically indicated.

After short-term administration of Actynox, it is not necessary to interrupt breastfeeding.

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

Driving and operating machinery

If you have received Actynox, without any other analgesic/sedative, for safety reasons, you should avoid driving, operating machinery, or performing complex tasks until you are fully recovered (at least 30 minutes).

Make sure your healthcare professional informs you if it is safe to drive.

Actynox will always be administered in the presence of familiar personnel with this form of medication. This will ensure that your Actynox supply is adequate for use and that the equipment has been installed correctly. While using Actynox, you will be monitored to ensure that it is administered safely. After completing treatment with Actynox, you must be supervised by competent personnel until you have recovered.

Always use this medication exactly as your doctor has instructed.

Your doctor must explain how to use Actynox, how Actynox works, and what effects result from its use. In case of doubt, consult your doctor again.

Actynox is normally inhaled through a facial mask connected to a special valve, which means that you have full control of the gas flow through your own breathing. The valve is only open during inspiration. Actynox can also be administered with a nasal mask.

Regardless of the mask used, you must breathe normally through regular breaths with the mask.

After completing treatment with Actynox, you must rest and recover until you feel mentally recovered.

Safety Precautions

If you use more Actynox than you should

It is very unlikely that you will receive an excess of gas, as you regulate the gas supply and the gas mixture is fixed (containing 50% nitrous oxide and 50% oxygen).

If you breathe more quickly than normal and thus receive more nitrous oxide than with normal breathing, you may feel clearly tired and notice that you have disconnected to some extent from your surroundings. In this case, you must immediately inform the medical personnel and interrupt administration.

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

Like all medications, this medication may produce adverse effects, although not all people will experience them.

Frequent(affect 1 to 10 users out of 100):

Dizziness, mild dizziness, euphoria, nausea, and vomiting.

Infrequent(affect 1 to 10 users out of 1,000):

Severe fatigue. Sensation of pressure in the middle ear, if you use Actynox for a prolonged period. This is due to Actynox increasing pressure in the middle ear.

Abdominal swelling, due to Actynox slowly increasing the volume of gas in the intestines.

Unknown Frequency(cannot be estimated from available data)

Effects on the bone marrow, which may cause anemia.

Effects on the nervous system, numbness and weakness sensations, usually in the legs.

This is due to nitrous oxide affecting the metabolism of vitamin B12and folate, and therefore inhibiting an enzyme: methionine synthase.

Respiratory depression. You may also experience headaches. Psychiatric effects, such as psychosis, confusion, anxiety, addiction.

Generalized seizures

Reporting Adverse Effects

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it is an adverse effect that does not appear in this prospectus. You can also report them directly through the Spanish System for Pharmacovigilance of Medicines for Human Use:www.notificaRAM.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medication.

Keep out of sight and reach of children.

Do not use this medication after the expiration date that appears on the label of the vial. The expiration date is the last day of the month indicated.

Store at a temperature between 0 °C and 50 °C. Do not freeze.

Full cylinders must be stored IN HORIZONTAL POSITION AT TEMPERATURES BETWEEN 10°C and 30°C for at least 48 hours before use, with valves closed.

Protected from impacts, falls, heat sources or ignition, adverse weather conditions, and low temperatures in particular

If it is suspected that Actynox has been stored in conditions too cold, the vials must be stored in horizontal position at a temperature above +10°C for at least 48 hours before use.

Keep the vial in a closed and reserved storage place for medicinal gases.

Different types of gas must be separated from each other.

Empty and full gas vials must be stored separately.

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Inhaling vapor may cause drowsiness and dizziness.

What Actynox contains

• The active principles are:

Nitrous oxide 50% (v/v) = medicinal laughing gas (chemical term: N2O) and oxygen 50% (v/v) = medicinal oxygen (chemical term: O2)

• Actynox does not contain other active principles.

Appearance of Actynox and contents of the container

Actynox is an colourless, odourless, tasteless gas, supplied in a gas cartridge with a valve to control the flow of gas. The cartridge may be made of steel or aluminium. Pharmaceutical dosage form: medicinal gas compressed

The cartridge head is marked white and blue (oxygen/nitrous oxide). The cartridge body is white (medicinal gas).

Steel or aluminium containers, filling pressure 185 bar:

2, 5, 10, 15 or 50 litres container sizes with a closing valve with or without an integrated pressure regulator and a standard connector.

185 bar filled cylinders contain approximately X cubic metres of gas at atmospheric pressure and 15°C according to the table below:

Only some container sizes may be commercially available.

Marketing authorisation holder

S.E. Carburos Metálicos, S.A.

Avda de la Fama,1

08940 – Cornella de Llobregat

Spain

Manufacturer

Laboratoires SOL France 8 rue du Compas

ZI les Bethunes

Rue du Compas

95310 Saint-Ouen-l’Aumône

France

This medicinal product is authorised in the member states of the European Economic Area with the following names:

Netherlands: Actynox, 50%/50% v/v medicinal gas, samengeperst

Belgium: Actynox, 50%/50% v/v, medicinaal gas, samengeperst

Portugal: Actynox, 50%/50% v/v

Spain: Actynox, 50%/50% v/v, gas comprimido medicinal

Czech Republic: Actynox 50%/50% V/V medicinální plyn, stlacený

Slovak Republic: Actynox 50% / 50% v/v medicinálny plyn stlacený

Date of the last revision of this leaflet: September 2019.

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This information is intended solely for healthcare professionals: DOES NOT MATCH THE APPROVED

Instructions for use

Special precautions should be taken when working with nitrous oxide. Nitrous oxide should be administered according to local guidelines.

Actynox should only be used in well-ventilated areas and where special equipment is available for extracting excess gas. If a gas extractor is used and good ventilation is ensured, high concentrations of laughing gas in the air can be avoided. High concentrations of laughing gas in the air can cause adverse effects on the health of personnel and people nearby. National guidelines exist for the concentration of laughing gas that should not be exceeded in the air, often expressed as TWA (time-weighted average), the mean value of a working day, and STEL (short-term exposure limit) during a shorter exposure.

These values should not be exceeded to ensure that personnel are not exposed to risks.

• The valve should be opened slowly and carefully.
• Close the equipment in case of fire, or if it is not being used.
• During use, the cartridge should be fixed in an appropriate support.
• Consider replacing the gas cartridge when the pressure in the cartridge has fallen to the point where the indicator on the valve is in the yellow field.
• When a small amount of gas remains in the cartridge, the valve should be closed.

It is essential to leave a little pressure in the cartridge to prevent the entry of contaminants.

• After use, the valve of the cartridge should be closed manually until it is tight. Release the pressure regulator or connection.

Further detailed information on this medicinal product is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS) http://www.aemps.gob.es

Cylinders of medicinal gas mixture of nitrous oxide – oxygen, are exclusively reserved for medicinal use.

WHAT YOU SHOULD KNOW BEFORE USING ACTYNOX

• The personnel using the cylinders should be trained in how to handle gases.
• Do not use any cylinder that has been exposed to negative temperatures.
• If signs of freezing appear on the cylinder, do not use it and return it to the pharmacy service.
• Do not manipulate any cylinder if the valve is not protected.
• Never use a cylinder that leaks.
• Never attempt to repair a damaged cylinder.
• Ensure the cylinders are properly secured (chains, etc.) to maintain them in a HORIZONTAL position and prevent them from falling accidentally.
• Never apply excessive force to fit a cylinder into a support.

PRECAUTIONS FOR THE HANDLER AND THEIR PATIENT

• Never position yourself in front of the outlet valve, position yourself on the opposite side of the pressure regulator at a certain distance behind the cylinder. Never expose the patient to the gas flow.
• Connect the equipment with clean and grease-free hands (without gloves and without using pliers).
• Do not use sprays (hair sprays, deodorants…), solvents (alcohol, gasoline…) on the material or nearby.
• Do not apply grease to the patient's face (vaseline, ointments, etc…).

ATTENTION

• Do not lubricate.
• Do not smoke.
• Do not place near an open flame.

And in particular:

1. Never introduce the gas into an apparatus that may have contained combustible materials and in particular greasy substances.
2. Never clean equipment containing gas, or taps, joints, accessories, closure devices with combustible products and in particular greasy substances.

• In case of leakage, close the defective valve, ventilate the room and evacuate it.
• In case of fire, the risk of toxicity increases due to the formation of nitrous oxide fumes.

INSTRUCTIONS FOR USE AND HANDLING OF CYLINDERS

The following rules must be respected in order to prevent accidents:

Connection:

• For cylinders equipped with a valve
• Open the valve slowly before connecting the pressure regulator to blow any dirt or foreign material out of the valve outlet. Always keep the interface between the cylinder and the pressure regulator clean.
• Ensure that the pressure regulator equipment is compatible with this mixture and that the pressure regulator joint is in good condition.
• Use pressure regulators specific to equimolecular mixtures of nitrous oxide – oxygen at 185 bar (two-phase pressure regulators equipped with special connectors according to standard regulations).
• Use a pressure regulator with a flow meter capable of reading pressures at least 1.5 times the maximum working pressure of the cylinder.
• For cylinders equipped with an integrated pressure regulator:
• For safety reasons, these cylinders can only be used with a folded tube connected to a specific connector with a blue and white control lock and connected to a demand valve, or to a flow meter equipped with a specific connector with a blue and white control lock.
• A specific connector for medicinal gas mixture of nitrous oxide – oxygen that meets national standards must be used.
• Never tighten the pressure regulator with pliers as it may damage the joint.
• Do not use an adapter connector to connect two devices that do not fit normally.
• If signs of freezing appear on the pressure regulator, check if the gas flows (inflated balloon) as the pressure regulator may be blocked.
• Ventilate the space (room, vehicle, etc.) after prolonged use and ensure the gas is evacuated in case of an accident or accidental leakage.

Opening the cylinder after connecting it:

• Follow the instructions on the label of the cylinder cap.
• Never use force to open the valve or to open it completely.
• Always open the valve slowly, gradually, to prevent cooling that may lead to the segregation of the mixture.
• Never suddenly pressurize the pressure regulator.
• Do not transfer gas under pressure from one cylinder to another.

After use:

• Close the valve of the cylinder after use, allow the pressure regulator reader to fall as the regulator is left open, then close the pressure regulator and unscrew the pressure regulator nut.
• Never empty the cylinder completely and always leave a minimum pressure of 10 bar.
• Keep empty cylinders in a VERTICAL position with their valves closed (to prevent corrosion due to humidity).