ACTYNOX 50%/50% MEDICINAL COMPRESSED GAS PULMONARY INHALATION

Contents of the leaflet

1. Introduction
2. What is Actynox and what is it used for
3. What you need to know before you use Actynox
4. Warnings and precautions
5. Using Actynox with other medicines
6. Pregnancy, breastfeeding, and fertility
7. Driving and using machines
8. How to use Actynox
9. Possible side effects
10. Storage of Actynox
11. Contents of the pack and other information
12. What Actynox contains
13. Appearance of Actynox and contents of the pack
14. This medicine is authorized in the Member States of the European Economic Area under the following names:
15. Date of last revision of this leaflet: September 2019.
16. This information is intended only forhealthcare professionals: DOES NOT MATCH THE APPROVED
17. Safety Instructions

Introduction

Package Leaflet: Information for the User

Actynox 50%/50% Compressed Medical Gas

Nitrous Oxide/Oxygen

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this leaflet, you may need to read it again. If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the Package Leaflet

1. What is Actynox and what is it used for
2. What you need to know before you use Actynox
3. How to use Actynox
4. Possible side effects
5. Storage of Actynox
6. Contents of the pack and other information

1. What is Actynox and what is it used for

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

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

The effects of Actynox

Nitrous oxide constitutes 50% of the gas mixture. Nitrous oxide has an analgesic effect, reduces the sensation of pain, and raises the pain threshold. Nitrous oxide also has a relaxing and slightly calming effect. These effects are produced by the action of nitrous oxide on the substances that send signals in your nervous system.

The effect of Actynox is lower in children under three years of age.

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

What is Actynox and what is it used for

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

2. What you need to know before you use Actynox

Do not use Actynox:

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

• Gases or gas bubbles in body cavities:If, as a result of a disease or for any other reason, it is suspected that there is air in the thorax outside the lungs, or gas bubbles in the blood, or in any other organ. For example, if you have dived with diving equipment 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 can expand and cause damage.
• Heart disease:If you have heart failure or severe impairment of cardiac function, since the mild relaxing effect of nitrous oxide on the heart muscle may further impair cardiac function.
• Central nervous system injury:If you have increased pressure in the brain, for example, as a result of a tumor or cerebral hemorrhage, since nitrous oxide may further increase pressure in the brain with a possible risk of damage.
• Vitamin deficiency:If you have been diagnosed with a vitamin B12 deficiency or a folic acid deficiency, but have not received treatment for it, since the use of nitrous oxide may worsen the symptoms caused by the vitamin B12 and folic acid 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 continuously, 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, inflammation in the ear, since Actynox may increase pressure in the middle ear.
• Vitamin deficiency:if you suspect you have a vitamin B12 deficiency or a folic acid deficiency, since the use of nitrous oxide may worsen the symptoms caused by the vitamin B12 and folic acid deficiency.
• The success rate is lower in children under 3 years of age.

Your doctor will decide if Actynox is suitable for your use.

Using Actynox with other medicines

Tell your doctor or pharmacist if you are using, have recently used, or might use any other medicines.

If you are taking other medicines that affect the brain or brain function, such as benzodiazepines (tranquilizers) or morphine-like medicines, you should inform your doctor. Actynox may increase the effects of these medicines. Actynox in combination with other sedatives or other medicines that affect the central nervous system increases the risk of side effects.

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

Pregnancy, breastfeeding, and fertility

Actynox can be used during pregnancy when 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 are planning to have a baby, ask your doctor or pharmacist for advice before using this medicine.

Driving and using machines

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

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

3. How to use Actynox

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

Always use this medicine exactly as your doctor has told you.

Your doctor should explain how to use Actynox, how Actynox works, and what effects result from its use. If you are unsure, consult your doctor again.

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

Regardless of the mask used, you should breathe normally through normal breaths with the mask.

After finishing treatment with Actynox, you should rest and recover until you feel you have mentally recovered.

Safety precautions

• It is strictly forbidden to smoke and be exposed to flames in the rooms where treatment with Actynox is carried out.
• Actynox is intended only for medical use.

If you use more Actynox than you should

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

If you breathe more quickly than normal and therefore receive more nitrous oxide than with normal breathing, you may feel clearly tired and notice that you have disconnected to some extent from your environment. In such a case, you should immediately inform the medical staff and interrupt administration.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Common(affect 1 to 10 users in 100):

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

Uncommon(affect 1 to 10 users in 1,000):

Severe fatigue. Feeling of pressure in the middle ear, if you use Actynox for a prolonged period. This is because Actynox increases pressure in the middle ear.

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

Frequency not known(cannot be estimated from the available data)

Effects on the bone marrow, which can cause anemia.

Effects on nerve function, sensations of numbness and weakness, usually in the legs.

This is because nitrous oxide affects the metabolism of vitamin B12 and folate, and thus inhibits an enzyme: methionine synthase.

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

Generalized convulsions

Reporting of side effects

If you experience any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly through the Spanish Medicines Monitoring System: www.notificaRAM.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Actynox

Keep out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the label of the batch. The expiry date is the last day of the month stated.

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

Full cylinders should be stored IN A HORIZONTAL POSITION AT TEMPERATURES BETWEEN 10°C AND 30°C FOR AT LEAST 48 HOURS BEFORE USE, WITH THE VALVES CLOSED.

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

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

Keep the cylinder in a closed and reserved storage area for medical gases.

The different types of gas should be separated from each other.

Empty and full gas cylinders should be stored separately.

.

Inhaling vapor can cause drowsiness and dizziness.

6. Contents of the pack and other information

What Actynox contains

• The active substances 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 any other active substances.

Appearance of Actynox and contents of the pack

Actynox is a colorless, odorless, tasteless gas, which is supplied in a gas cylinder with a valve to control the gas flow. The cylinder may be made of steel or aluminum. Pharmaceutical form: compressed medical gas

The tip of the gas cylinder is marked in white and blue (oxygen/nitrous oxide). The body of the gas cylinder is white (medical gas).

Steel or aluminum containers, filling pressure 185 bar:

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

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

Not all pack sizes may be marketed.

Marketing authorization 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 medicine is authorized in the Member States of the European Economic Area under the following names:

Netherlands: Actynox, 50%/50% v/v medicinaal 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

Slovakia: Actynox 50% / 50% v/v medicinálny plyn stlacený

Date of last revision of this leaflet: September 2019.

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This information is intended only forhealthcare professionals: DOES NOT MATCH THE APPROVED

Safety Instructions

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

Actynox should only be used in well-ventilated areas and where there is special equipment to extract excess gas. If an extraction system is used and good ventilation is ensured, high atmospheric concentrations of laughing gas in the air are avoided. High concentrations of laughing gas in the air can cause adverse health effects on personnel and people nearby. There are national guidelines for the concentration of laughing gas that should not be exceeded in the ambient air, the so-called "hygienic limit values", often expressed according to the TWA (time-weighted average), the average value of a working day and the average STEL (short-term exposure limit) during shorter exposure.

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

• The valve must be opened slowly and carefully.
• Close the equipment in case of fire, or if it is not being used.
• During use, the cylinder must be fixed in a suitable support.
• It should be considered to replace the gas cylinder when the pressure in the cylinder has dropped to the point where the valve indicator is in the yellow field.
• When a small amount of gas remains in the cylinder, the valve must be closed.

It is important to leave a little pressure in the cylinder to prevent the entry of contaminants.

• After use, the cylinder valve must be closed manually until it is tight. Depressurize the regulator or connection.

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

Medical mixture cylinders of equimolecular nitrous oxide - oxygen are exclusively reserved for medicinal use.

WHAT YOU SHOULD KNOW BEFORE USING ACTYNOX

• Personnel using the cylinders must be trained in handling 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 handle any cylinder if the valve is not protected.
• Never use a cylinder that leaks.
• Never attempt to repair a damaged cylinder.
• Secure the cylinders properly (chains, etc.) in order to keep them in a HORIZONTAL POSITION and prevent them from falling accidentally.
• Never use 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 near it.
• Do not anoint the patient's face with greases (vaseline, ointments, etc...).

WARNING

• Do not lubricate.
• Do not smoke.
• Do not place near a flame.

And in particular:

1. Never introduce the gas into a device that may have contained combustible materials and in particular greasy substances.
2. Never clean the equipment that contains the gas, nor taps, joints, accessories, or closing devices with combustible products and in particular with greasy substances.

• In case of a leak, close the faulty valve, ventilate the room, and evacuate it.
• In case of fire, the risk of toxicity increases due to the formation of nitrous 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 particles or foreign material out of the valve outlet. Always keep the interface between the cylinder and the pressure regulator clean.
• Make sure the pressure regulation equipment is compatible with this mixture and that the pressure regulator gasket is in good condition.
• Use pressure regulators specifically designed for 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 lock control and connected to a demand valve, or to a flow meter equipped with a specific connector with a blue and white lock control.
• A specific connector for medicinal nitrous oxide - oxygen mixture that meets national standards must be used.
• Never tighten the pressure regulator with pliers as it may damage the gasket.
• Do not use a connector adapter 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 that the gas is evacuated in case of an accident or accidental leak.

Opening the cylinder after connection:

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

After use:

• Close the cylinder valve after use, allow the pressure regulator reader to drop by leaving the regulator open, then close the pressure regulator and unscrew the regulator thread.
• Never completely empty the cylinder 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).