NINOXAN 50%/50% MEDICINAL COMPRESSED GAS

2. What you need to know before you use Ninoxan

Do not use Ninoxan:

Before using Ninoxan, you should tell your doctor if you have any of the following symptoms/conditions:

• Gas-filled cavities or gas bubbles: if, as a result of an illness, or for any other reason, you suspect that there is air in your pleural cavities outside the lungs, or gas bubbles in the blood, or in any other organ (e.g., if you have dived with diving equipment and may have gas bubbles in the blood (decompression sickness); or if you have received a gas injection into the eye, e.g., for a retinal detachment, or similar) these gas bubbles can expand and cause damage.

• Heart disease: if you have heart failure or poor heart function, as the mild relaxing effect of nitrous oxide on the heart muscle may worsen heart function.

• After treatment with a heart-lung machine or coronary bypass.

• Central nervous system injury: if you have increased pressure in the brain, e.g., as a result of a tumor or cerebral hemorrhage, nitrous oxide may further increase brain pressure with potential risk of damage.

• Vitamin deficiency: If you have a diagnosed but untreated vitamin B12 deficiency or folic acid deficiency, the use of nitrous oxide may worsen the symptoms caused by the vitamin B12 and folic acid deficiency.

• Intestinal dilation (ileus or intestinal obstruction): if you have severe abdominal discomfort: if there are symptoms that may indicate ileus, Ninoxan may further increase intestinal dilation.

• In patients with facial injuries, the use of masks may present difficulties or risks.

• Decreased level of consciousness or impaired ability to cooperate and follow instructions, due to the risk that prolonged sedation with nitrous oxide may affect natural protective reflexes.

Warnings and precautions

Talk to your doctor or nurse before receiving Ninoxan if you:

• have abused drugs/medicines because there is a greater risk of developing dependence on nitrous oxide if it is taken repeatedly. Your doctor will decide if treatment with Ninoxan is possible in your case.

Talk to your doctor before starting to use Ninoxan.

Tell your doctor if you have any of the following symptoms:

• Ear discomfort: e.g., ear inflammation, as Ninoxan may increase pressure in the middle ear.

• Vitamin deficiency: if you suspect you have a vitamin B12 or folic acid deficiency, e.g., if you have reduced intake or intake of vitamin B12 or folic acid, or you have a genetic disorder that affects the metabolism of these vitamins or if you are immunocompromised. The use of nitrous oxide may worsen the symptoms caused by the vitamin B12 and folic acid deficiency.

Your doctor will decide if Ninoxan is indicated for your use.

Repeated or prolonged use of nitrous oxide may increase the risk of vitamin B12 deficiency, which can cause damage to the bone marrow or nervous system. Your doctor may initiate blood tests before and after treatment to evaluate the consequences of possible vitamin B12 deficiency.

Children

Ninoxan should not be used in children under 1 month of age.

Your doctor will decide if it is appropriate to use Ninoxan.

Using Ninoxan with other medicines

Tell your doctor or pharmacist that you are taking, have recently taken, or might take any other medicines.

If you are taking other medicines that affect the brain or brain function, e.g., benzodiazepines (tranquilizers) or morphine-like medicines, you should inform your doctor. Ninoxan may increase the effects of these medicines. Ninoxan, taken together with other sedatives or 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 the treatment of rheumatoid arthritis), bleomycin (cancer treatment), nitrofurantoin, and other antibiotics (infection treatment), or amiodarone (heart disease treatment). Ninoxan increases the side effects of these medicines.

Pregnancy and 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.

Pregnancy

Ninoxan can be used during pregnancy if your doctor considers it clinically necessary. It can also be used during childbirth.

If Ninoxan is used near childbirth, your baby should be monitored for possible side effects.

Breastfeeding

Ninoxan can be used during breastfeeding, but it should not be used while breastfeeding.

Driving and using machines:

Ninoxan has a sedative effect, which may affect your mind and body. For safety reasons, you should avoid driving, operating machinery, or performing complex tasks until you have fully recovered. Check with your healthcare professional when they think you are fully recovered.

3. How to use Ninoxan

Ninoxan should always be administered in the presence of personnel familiar with this type of medicine and equipment. During the period when you use Ninoxan, both you and the administration of the medicine should be monitored to ensure that it is administered safely. After completing treatment, you should be monitored by competent personnel until you have recovered.

Your doctor should explain how to use Ninoxan, how Ninoxan works, and what effects result from its use.

Follow exactly the administration instructions of this medicine indicated by your doctor. In case of doubt, ask your doctor.

Normally, Ninoxan is inhaled through a mask with a special valve, having full control of the gas flow through your own breathing. The valve is open only during inspiration. Ninoxan can also be administered with a nasal mask.

Regardless of which mask is used, you should breathe normally, with normal breaths in the mask. Ideally, you should hold the mask yourself.

You should start using Ninoxan shortly before the analgesic effect is required and continue during the painful process. The effect of Ninoxan disappears a few minutes after stopping inhalation.

After stopping the use of Ninoxan, you should rest and recover until you feel mentally recovered.

Safety measures:

• Smoking and the presence of flames are strictly prohibited in the room where Ninoxan treatment takes place.
• Ninoxan is exclusively for medical use.

Use in children

Ninoxan should not be used in children under 1 month of age.

If you use more Ninoxan than you should:

It is unlikely that you will receive an excess of gas, as the gas application is controlled by your own breathing and the gas mixture is fixed (with 50% nitrous oxide and 50% oxygen).

If you breathe faster than normal, receiving more nitrous oxide than with normal breathing, you may feel noticeably tired and lose contact with your surroundings to some extent. In such a case, you should immediately inform the medical staff and interrupt the inhalation of Ninoxan.

If you have any further questions on the use of this product, ask your doctor or healthcare professional.

In case of overdose or accidental ingestion, consult the Toxicological Information Service.

Telephone 91 562 04 20.

4. Possible side effects

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

The following side effects have been reported:

Side effects and their frequency:

Frequent(may affect 1 in 10 patients):

• Dizziness, vertigo, feeling of fainting.
• Mild headache.
• Euphoria.
• Nausea and vomiting.

Uncommon(may affect 1 in 100 patients):

• Severe fatigue.
• Feeling of pressure in the middle ear, if Ninoxan is used for a prolonged period.
• Abdominal bloating, because Ninoxan slowly increases the volume of intestinal gases.

Muy raros(may affect 1 in 10,000 patients):

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

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

• Effects on the bone marrow, which can cause anemia. Low levels of white blood cells.
• Psychiatric effects, such as psychosis, confusion, and anxiety.
• Respiratory depression.
• Headache.
• Generalized convulsions.
• Addiction.
• Effects on nerve function, sensations of numbness and weakness, usually in the legs.

Reporting of side effects

If you experience side effects, talk to your doctor, even if they are not listed in this leaflet.

You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Ninoxan

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

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

The mixture is unstable below -5°C. Do not store below -5°C. If you suspect that Ninoxan has been stored at temperatures below -5°C, the cylinders should be placed in a horizontal position at a temperature above +10°C for at least 48 hours before use.

When used in emergency vehicles, the cylinders should be protected from cold and firmly secured both inside and outside the vehicle.

Store the cylinder in a storage area reserved for medical gases.

Different types of gases should be separated from each other. Full and empty gas cylinders should be stored separately.

No smoking. Do not expose to strong heat.

The gas vapors can cause drowsiness and dizziness.

Keep away from combustible materials.

If there is a risk of fire, move it to a safe place.

Keep the cylinder clean, dry, and free of oil and grease.

Keep the cylinder in a vertical position.

Make sure the cylinder has not been damaged or dropped.

It should be stored and transported with the valves closed.

6. Container Contents and Additional Information

Ninoxan Composition:

• The active principles are:

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

• Ninoxan does not contain any other ingredients.

Product Appearance and Container Contents

Ninoxan is a colorless, odorless gas, supplied in a steel or aluminum cylinder with a valve to control gas flow.

The cylinders are identified by specific colors (white body with blue and white shoulder, with two horizontal bands being blue the lower one).

Containers

Aluminum cylinder with integrated valve or standard residual pressure valve (VPR):

• 2-liter filled to 170 bar which provides 0.56 m3 of gas at atmospheric pressure and 15°C.
• 5-liter filled to 170 bar which provides 1.4 m3 of gas at atmospheric pressure and 15°C.
• 10-liter filled to 170 bar which provides 2.8 m3 of gas at atmospheric pressure and 15°C

Seamless steel cylinder with integrated valve or standard VPR:

• 5-liter filled to 170 bar which provides 1.4 m3 of gas at atmospheric pressure and 15°C.
• 10-liter filled to 170 bar which provides 2.8 m3 of gas at atmospheric pressure and 15°C

Seamless steel cylinder with standard VPR:

• 50-liter filled to 170 bar which provides 14 m3 of gas at atmospheric pressure and 15°C.

Only some container sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder:

NIPPON GASES ESPAÑA S.L.U.

C/Orense, 11 28020 Madrid. Spain

Manufacturer:

NIPPON GASES ESPAÑA S.L.U.

Calle Embajadores, 474

28053 Madrid, Spain

Date of the Last Revision of this Prospectus: 06/2020

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

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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 can cause addiction. Caution should be exercised in healthcare professionals with occupational exposure to nitrous oxide.

Ninoxan should only be used in well-ventilated areas and where there is special equipment to extract excess gas. Using an extraction system and ensuring good ventilation, high atmospheric concentrations of nitrous oxide in the air can be avoided. High concentrations of nitrous oxide in the air can cause adverse health effects on personnel and people in the surrounding area of administration. There are national values for the concentration of nitrous oxide in the air. These values should not be exceeded to ensure that personnel are not exposed to risks.

The so-called "threshold limit values" for occupational exposure to chemicals are often expressed as: TWA (time-weighted average or daily weighted average), which is the average value during a working day, and STEL (short-term exposure limit or short-term exposure limit), which is the average value during a shorter exposure.

Ninoxan is an unstable mixture below -5°C. Lower temperatures can cause temporary liquefaction of nitrous oxide, which would result in the inhalation of an unequal mixture, with an excess of oxygen at the start of administration (mixture with little analgesic effect) and too much nitrous oxide at the end (hypoxic mixture) of inhalation.

If it is suspected that the cylinder has been stored below -5°C, the cylinders should be stored in a horizontal position at a temperature above 10°C for at least 48 hours before use. It is recommended to shake the cylinder completely by inverting it at least three consecutive times to ensure homogenization before use.

Store the cylinders in a storage area reserved for medicinal gases. Different types of gas should be separated from each other. Full and empty gas cylinders should be stored separately.

When used in emergency service vehicles, the cylinders should be protected from cold and firmly secured both inside and outside the vehicle.

Other instructions:

• Keep away from combustible materials. Do not smoke.
• Open the valve slowly and carefully. Never use oils or greases, even in case of difficulty opening the valve or if the regulator is difficult to connect. Never force the valve, use only compatible devices and gaskets with the specific gas mixture and oxidizing gases. Never use a tool to connect a manual pressure/flow regulator, as this may damage the coupling.
• Close the cylinder valve in case of fire, or if it is not working. Store and transport cylinders always with the valves closed, even when they are empty.
• During use of the cylinder, it should be fixed with a suitable support. Keep the containers in a vertical position, however, the cylinders should be stored in a horizontal position when it is suspected that the cylinder has been stored at temperatures below -5°C.
• The gas cylinder should be replaced when the pressure in the cylinder has dropped to a point where the valve indicator is within the yellow field.
• When a small amount of gas remains in the cylinder, the cylinder valve should be closed. It is important that a small amount of pressure remains in the cylinder to prevent the entry of contaminants. Keep full containers separate from empty ones.
• After use, the cylinder valve should be closed by hand. Depressurize the regulator or connection.

For more details, read the Summary of Product Characteristics (SPC) or contact the supplier.