NODOLOX 50%/50% MEDICINAL COMPRESSED GAS

2. What you need to know before you use Nodolox

Do not use Nodolox:

Before using this medicine, you must 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, 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, as 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, as nitrous oxide may 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, as 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 Nodolox may further increase intestinal dilation.

Warnings and precautions

Consult your doctor or pharmacist before using Nodolox:

If you need to use this medicine for more than 6 hours in a row, the healthcare professional will perform routine blood tests to ensure that Nodolox has not affected your blood count or how your body uses vitamin B12.

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

• Ear problems:such as inflammation in the ear, as this medicine may increase pressure in the middle ear.
• Vitamin deficiency:if you suspect you have a vitamin B12 deficiency or a folic acid deficiency, as the use of nitrous oxide may worsen the symptoms caused by the vitamin B12 and folic acid deficiency.
• If you have or have had drug addiction, as there is a high risk of dependence on nitrous oxide if it is administered repeatedly. Your doctor will decide if treatment with nitrous oxide is possible in your case.

Prolonged or repeated use of nitrous oxide may increase the risk of vitamin B12 deficiency, which can cause damage to the bone marrow or nervous system. The use of nitrous oxide should be accompanied by close clinical supervision and hematological monitoring 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 of age.

Nodolox can be used in children who can follow instructions on how to use the equipment. In the treatment of smaller 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 medicine should not be used in children under 1 month of age.

Other medicines and Nodolox

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. Nitrous oxide may increase the effects of these medicines. Nodolox 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). Nodolox increases the adverse effects of these medicines.

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 medicine.

Pregnancy

Some data indicate that 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

It is not known if medicinal nitrous oxide is excreted in breast milk. It is not necessary to interrupt breastfeeding after a short period of administration.

Driving and using machines

Do not drive or operate tools or machines after receiving Nodolox, as this medicine may affect your reaction ability. Your doctor will tell you how long you should wait before driving or using machines again.

3. How to use Nodolox

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

Always use this medicine exactly as your doctor has told you. The doctor should explain how to use Nodolox, how Nodolox works, and what effects result from its use. If you are in doubt, consult your doctor again.

Nodolox is usually inhaled through a facial 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. Nodolox can also be administered with a nasal mask.

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

After finishing treatment with this medicine, 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 Nodolox is carried out.
• Nodolox is intended only for medical use.

If you use more Nodolox 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 (contains 50% nitrous oxide and 50% oxygen).

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

If you have any further questions about 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(may affect up to 1 in 10 people): Dizziness, mild dizziness, euphoria, nausea, and vomiting.

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

This is because Nodolox increases the pressure in the middle ear.

Abdominal swelling, due to Nodolox 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 with unknown frequency.

Reporting of side effects

If you experience any side effects, talk to your doctor or pharmacist, even if it is a side effect not listed in this leaflet. You can also report side effects directly through the Spanish Pharmacovigilance System for Human Use Medicines: www.notificaRAM.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Nodolox

Keep this medicine out of the sight and reach of children.

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

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

If it is suspected that the medicine has been stored in too cold conditions, the cartridges should 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 can cause fire. Do not smoke or light a flame near Nodolox.

Do not expose to intense heat.

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

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

Different types of gas should be separated from each other. Empty and full gas cartridges should be stored separately.

Store and transport with the valves closed.

Ensure that the cartridge is not hit or dropped. Inhaling vapor can cause drowsiness and dizziness.

6. Contents of the pack and other information

Composition of Nodolox

The active substances are:

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

This medicine does not contain other active substances or excipients.

Appearance of the product and contents of the pack

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

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

Package 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).

Not all package sizes may be marketed.

Marketing authorization holder

OXIGEN SALUD, S.A.

Carretera de Rubí 141-143

08174 Sant Cugat del Vallès (Barcelona)

Spain

Manufacturer

OXIGEN SALUD, S.A.

Polígono Industrial, Calle A, Parcela 63.

09320 Madrigal del Monte (Burgos)

Date of last revision of this leaflet: May 2019

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This information is intended only for healthcare professionals:

Safety instructions

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. Healthcare professionals with occupational exposure to nitrous oxide should be cautious.

Nodolox 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 can be avoided. There are national guidelines for the concentration of laughing gas that should not be exceeded in the ambient air, often expressed as TWA (time-weighted average), the average value of a working day, and the STEL (short-term exposure limit) value during 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 in use.
• During use, the cartridge should be fixed in a suitable holder.
• Consider replacing the gas cartridge when the pressure in the cartridge has dropped to the point where the valve indicator is in the yellow field.
• When a small amount of gas remains in the cartridge, the valve should be closed.
• It is important to leave some pressure in the cartridge to avoid the entry of contaminants.
• After use, the valve of the cartridge should be manually closed until it is tight.
• Depressurize the regulator or connection.

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