Leaflet: information for the user

Nodolox 50%/50% compressed medicinal 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 doubts, consult your doctor or pharmacist.
• This medicine has been prescribed only for you, 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 adverse effects, consult your doctor or pharmacist, even if they are not listed in this leaflet. See section 4.

1. What Nodolox is and for what it is used

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

3. How to use Nodolox

4. Possible adverse effects

5. Storage of Nodolox

6. Contents of the container and additional information

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

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

Nodolox effects

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 this medication 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 Nodolox and what is it used for

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

Do not use Nodolox:

Before using this medication, 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 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 a 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 been diagnosed with a vitamin B12 deficiency or a folate deficiency, but have not received treatment for it, since the use of nitrous oxide may worsen the symptoms caused by vitamin B12 and folate deficiency.
• Intestinal obstruction:If you have severe abdominal discomfort: symptoms that may indicate intestinal obstruction, then Nodolox may further increase intestinal dilation.

Warnings and precautions

Consult your doctor or pharmacist before using Nodolox:

If you need to use this medication for more than 6 hours consecutively, the healthcare professional will perform routine blood tests to ensure that Nodolox 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 this medication may increase middle ear pressure.
• Vitamin deficiency:if you suspect that you have a vitamin B12 deficiency or a folate deficiency, since the use of nitrous oxide may worsen the symptoms caused by vitamin B12 and folate deficiency.
• If you have or have had a history of addiction to medications, since there is a high risk of generating dependence on nitrous oxide if it is administered repeatedly. Your doctor will decide if nitrous oxide treatment is possible in your case.

The prolonged or repeated use of nitrous oxide may increase the risk of vitamin B12 deficiency, which may cause damage to the bone marrow or nervous system. The use of nitrous oxide should be accompanied by close clinical supervision and hematological controls to evaluate the consequences of a possible vitamin B12 deficiency.

Your doctor will decide if Nodolox is suitable for you.

Children

The success rate is lower in children under 3 years old.

Nodolox can be used in children who can follow instructions on how to use the equipment. In the treatment of younger children, or in other patients who are not able to follow instructions, administration should be carried out with the help of a healthcare professional.

This medication should not be used in children under 1 month old.

Other medications and Nodolox

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 should inform your doctor. Nitrous oxide may increase the effects of these medications. Nodolox in combination with other sedatives, or other medications that affect the central nervous system, increases the risk of adverse effects.

You should 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). Nodolox increases the adverse effects of these medications.

Pregnancy, breastfeeding, and fertility

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

Pregnancy

Some data indicate that the short-term use of nitrous oxide during pregnancy does not pose a greater risk of congenital malformations. In isolated cases, nitrous oxide may cause respiratory problems in newborns.

Breastfeeding

The excretion of nitrous oxide medicinal in breast milk is unknown. It is not necessary to interrupt breastfeeding after a short period of administration.

Driving and operating machines

Do not drive or operate tools or machines after receiving Nodolox, as this medication may affect your reaction time. Your doctor will indicate how long you should wait before driving or operating machines.

Nodolox will be administered at all times in the presence of familiar personnel with this type of medicine. The personnel will ensure that Nodolox can be used and that the equipment has been installed correctly. While using this medication, you will be monitored to ensure that it is administered safely. After completing treatment with Nodolox, you will be supervised by competent personnel until you have recovered.

Use this medication exactly as your doctor has instructed. The doctor must explain how to use Nodolox, how Nodolox works, and what effects result from its use. In case of doubt, consult your doctor again.

Nodolox 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. Nodolox can also be administered with a nasal mask.

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

After completing treatment with this medication, you should rest and recover until you feel mentally recovered.

Safety Precautions

• Smoking and exposure to flames in rooms where Nodolox treatment is performed are strictly prohibited.
• Nodolox is intended only for medicinal use.

If You Use More Nodolox Than You Should

It is highly 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 faster 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 questions 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(may affect up to 1 in 10 patients/people): Dizziness, mild dizziness, euphoria, nausea, and vomiting.

Infrequent(may affect up to 1 in 100 patients/people): Severe fatigue. Sensation of pressure in the middle ear, if you use Nodolox for a prolonged period.

This is due to Nodolox increasing pressure in the middle ear.

Abdominal swelling, due to Nodolox 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 with an unknown frequency.

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 informationon the safety of this medication.

Keep this medication out of the 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.

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

Keep away from combustible materials.

Contact with combustible materials may cause fire. Do not smoke or ignite a flame near Nodolox.

Do not expose to intense heat.

If there is a risk of fire, move the vial to a safe location. Keep the vial clean, dry, and free of oil and grease.

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

Different types of gas must be separated from each other. Empty and full gas vials must be stored separately.

Store and transport with valves closed.

Ensure that the vial is not dropped or hit. Inhaling vapor may cause drowsiness and dizziness.

Composition of Nodolox

The active principles are:

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

This medicine does not contain other active principles or excipients.

Aspect of the product and content of the packaging

This medicine is an odorless, tasteless, colorless gas, supplied in a gas cartridge with a valve to control the flow of gas. The cartridge may be made of steel or aluminum.

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

Container sizes in liters (170 bar): 0.75 L, 1 L, 1.4 L, 1.6 L, 2 L, 2.5 L, 2.75 L, 3 L, 3.5 L, 4 L, 4.55 L, 4.7 L, 5 L, 6.7 L, 7 L, 10 L, 10.7 L, 13 L, 13.4 L, 15 L, 20 L, 30 L, 40 L, 50 L, blocks of cartridges 600 L (12 x 50 L) and 900 L (18 x 50 L).

Only some container sizes may be commercially available.

Holder of the marketing authorization

OXIGEN SALUD, S.A.

Carretera de Rubí 141-143

08174 Sant Cugat del Vallès (Barcelona)

Spain

Responsible for manufacturing

OXIGEN SALUD, S. A.

Polígono Industrial, Callea A, Parcela 63.

09320 Madrigal del Monte (Burgos)

Date of the last review of this prospectus: May 2019

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This information is intended solely for healthcare professionals:

Instructions for safety

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

Repeated administration or exposure to nitrous oxide may lead to addiction. Caution should be exercised in healthcare professionals with occupational exposure to nitrous oxide.

Nodolox should be used only in well-ventilated areas with specialized equipment for extracting excess gas. If a gas extractor system is used and good ventilation is ensured, high atmospheric concentrations of laughing gas in the air can be avoided. High concentrations of laughing gas in the air may cause adverse health effects on personnel and nearby individuals. National guidelines exist for the concentration of laughing gas that should not be exceeded in the air environment, often expressed as "hygienic limits", usually stated as TWA (time-weighted average), the mean value of a working day, and the STEL (short-term exposure limit) value 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 a fire, or if it is not in use.
• During use, the cartridge should be fixed to an appropriate support.
• The cartridge should be replaced 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 some 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.
• Depressurize the regulator or connection.

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