Prospect: information for the user

NINOXAN50%/50% medicinal compressed gas.

Nitrous oxide / Oxygen

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

• Keep this prospect, as you may need to read it again.
• If you have any doubts, consult your doctor or pharmacist.
• This medicine has been prescribed only to you and should not be given to other people even if they have the same symptoms as you, as it may harm them.
• If you experience adverse effects, consult your doctor or pharmacist, even if they do not appear in this prospect.See section 4

1.What isNinoxanand for what it is used

2.What you need to know before starting to useNinoxan

3.How to useNinoxan

4.Possible adverse effects

5.Storage ofNinoxan

6.Contents of the package and additional information

Ninoxancontains a prepared mixture of nitrous oxide (“medicinal laughing gas,” N2O) and oxygen (medical oxygen, O2), 50% of each, and must be used by breathing the gas mixture.

The effects of Ninoxan:

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

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

When to use Ninoxan:

Ninoxanmust be used when a rapid onset and resolution analgesic effect is desired for mild to moderate pain of limited duration.

Ninoxanproduces analgesic effect after a few inhalations and the analgesic effect decreases within minutes after its use ceases.

Children:

Ninoxanmay be used in children over 1 month of age

Do not use Ninoxan:

Before usingNinoxanyou 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 may suspect that there is air in your pleural cavities outside the lungs, or gas bubbles in the blood, or in any other organ (for example, if you have been scuba diving and may have gas bubbles in the blood (decompression sickness); or if you have received any gas intraocular injection, for example, for a retinal detachment, or similar) these gas bubbles may expand and cause damage.

•Heart disease:If you have heart failure or a poor heart function, since the mild relaxing effect of nitrous oxide on the heart muscle may further impair heart function.

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

•Central nervous system injury:If you have high blood pressure, for example, as a result of a tumor or cerebral hemorrhage, nitrous oxide may increase blood pressure further with potential risk of damage.

•Vitamin deficiency:If you have a diagnosed but untreated deficiency of vitamin B12, or a deficiency of folic acid, the use of nitrous oxide may worsen the symptoms caused by vitamin B12and folic acid deficiency.

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

•In patients with facial injuriesthe use of masks may present difficulties or risks.

•Decreased level of consciousnessor deterioration of the 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 or have had drug/medication abuse because there is a greater risk of developing dependence on nitrous oxide if you take it repeatedly. Your doctor will decide if treatment with Ninoxan is possible in your case

Consult your doctor before starting to useNinoxan

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

• Ear discomfort: For example, ear inflammation, sinceNinoxanmay increase middle ear pressure.

•Vitamin deficiency:If you suspect having a deficiency of vitamin B12or a deficiency of folic acid, for example,if your intake or taking of vitaminB12or folic acid has been reduced, or if you have a genetic disorder affecting the metabolism of these vitamins or if you are immunocompromised.Ninoxanmay worsen the symptoms caused by vitamin B12and folic acid deficiency.

Your doctor will decide ifNinoxanis indicated for use

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

Children

Ninoxanshould not be used in children under 1 month of age.

Your doctor will decide if it is appropriate to useNinoxan

Use of Ninoxan with other medications

Inform your doctor or pharmacist that you are taking, have taken recently, or may need to take any other medication.

If you are taking other medications that affect the brain or brain functions, for example, benzodiazepines (tranquilizers) or morphine-type medications, you must inform your doctor.Ninoxanmay increase the effects of these medications.Ninoxan, taken together with other sedatives or medications that affect the central nervous system, increases the risk of side effects.

You must also inform your doctor if you are taking medications that contain methotrexate (for example, for the treatment of rheumatoid arthritis), bleomycin (cancer treatment), nitrofurantoin and other antibiotics (infection treatment) or amiodarone (heart disease treatment).Ninoxanmay increase the side effects of these medications.

Pregnancy and lactation:

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

Pregnancy

Ninoxanmay be used during pregnancy if your doctor considers it clinically necessary. It may also be used during delivery.

If Ninoxan is used near delivery, your baby should be observed for possible adverse effects.

Lactation

Ninoxanmay be used during breastfeeding, but it should not be used at the time of breastfeeding.

Driving and operating machines:

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

Ninoxanmust be administered always in the presence of familiar personnel with this type of medication and equipment. During the period in which you useNinoxan, both you and the medication administration must be monitored to ensure that it is administered safely. After completing treatment, you must be monitored by competent personnel until you have recovered.

Your doctor must explain to you how to useNinoxan, how it worksNinoxan, and what effects result from its use.

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

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

Regardless of which mask is used, you must breathe normally,with normal breaths in the mask. It is ideal to hold the mask yourself.

Youmust begin to useNinoxanbefore theanesthetic effectis requiredandcontinueduring the pain process.The effect ofNinoxandisappearsafew minutesafter the interruptionoftheinhalation.

After stopping the use ofNinoxan, you must rest and recover until you feel mentally recovered.

Safety Precautions:

• Smoking and the presence of flames are strictly prohibited in the room where treatment withNinoxantakes place.

•Ninoxanis exclusively for medicinal use.

Use in Children:

Ninoxanmust 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, since 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 more quickly than normal, receiving thus more nitrous oxide than with normal breathing, you may feel noticeably tired and lose some contact with your surroundings. In this case, you must immediately inform the medical staff and interrupt the inhalation ofNinoxan.

If you have any additional questions about 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.

Like all medications,Ninoxanmay cause adverse effects, although not everyone will experience them.

The following adverse effects have been reported:

Adverse effects and their frequency:

Frequent(may affect 1 in 10 patients):

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

Rare(may affect 1 in 100 patients):

• Severe fatigue.
• Sensation of pressure in the middle ear, ifNinoxanis used for a prolonged period.
• Abdominal swelling, becauseNinoxangradually increases the volume of intestinal gases.

Very rare(may affect 1 in 10,000 patients):

• Nervous system effects, numbness and weakness sensations, usually in the legs.

Unknown frequency(cannot be estimated from available data):

• Bone marrow effects, which may cause anemia. Low white blood cell levels
• Psychiatric effects, such as psychosis, confusion, and anxiety.
• Respiratory depression.
• Headache.
• Generalized seizures
• Dependence
• Nervous system effects, numbness and weakness sensations, usually in the legs.

Reporting Adverse Effects

If you experience adverse effects, consult your doctor, even if they are not listed in this prospectus.

You can also report them directly through the national notification system included in theAppendix V.By reporting adverse effects, you can contribute to providing more information on 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 cartridge. The expiration date is the last day of the month indicated.

The mixture is unstable below-5ºC. Do not store it at temperatures below-5°C. If you suspect thatNinoxanhas been stored at temperatures below-5ºC, the cartridges should be placed in a horizontal position at a temperature greater than +10 ºCfor at least 48 hours before use.

When used in emergency services vehicles, the cartridges must be protected from the cold and securely fastened both inside and outside the vehicle.

Store the cartridge in a designated storage area for medical gases.

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

Do not smoke. It should not be exposed to strong heat.

The vapors of the gas may cause drowsiness and dizziness

It must be kept away from flammable materials.

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

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

Keep the cartridge in a vertical position.

Ensure that the cartridge has not suffered impacts or falls.

It must be stored and transported with the valves closed.

Composition of Ninoxan:

- The active principles are:

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

-Ninoxandoes not contain any other ingredient.

Appearance of the product and contents of the container

Ninoxanis an odorless, colorless gas that is supplied in a steel or aluminum cylinder with a valve to control the flow of gas.

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

Containers

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

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

Steel cylinder without welding with integrated valve or normal VPR valve:

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

Steel cylinder without welding with normal VPR valve:

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

Only some sizes of containers may be commercially available.

Holder of the marketing authorization and responsible for manufacturing

Holder of the marketing authorization:

NIPPON GASES ESPAÑA S.L.U.

C/Orense, 11 28020 Madrid. Spain

Responsible for manufacturing:

NIPPON GASES ESPAÑA S.L.U.

Calle Embajadores, 474

28053 Madrid, Spain

Date of the last review of this prospectus: 06/2020

The detailed information of this medicine is available on the website of the Spanish Agency for Medicines and Medical Devices (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 may cause addiction. Caution should be exercised in healthcare professionals with occupational exposure to nitrous oxide.

Ninoxanshould only be used in well-ventilated areas with special equipment for extracting excess gas. Using an extractor system and ensuring good ventilation, high atmospheric concentrations of nitrous oxide 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 the administration site. National values for nitrous oxide concentrations in the air exist. These values should not be exceeded to ensure that personnel are not exposed to risks.

The so-called "occupational exposure limits" for chemicals are often expressed as: TWA (time weight averageor daily average), which is the average value during a working day, and STEL (shortterm exposure limitor short-term exposure limit), which is the average value during a shorter exposure.

Ninoxanis unstable below -5°C. Temperatures below this may cause temporary liquefaction of nitrous oxide, which would lead to inhalation of the unequal mixture, with an excess of oxygen at the beginning 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 agitate the cylinder completely by inverting it at least three times consecutively to ensure homogenization before using it.

Store the cylinders in a reserved storage area 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 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 for connection and joints with the specific gas mixture and oxidizing gases.Never use a tool to connect a pressure/flow regulator manual connection, as this may damage the coupling.
• Close the cylinder valve in case of fire, or if it is not functioning. Store and transport the cylinders always with the valves closed, even when empty.
• During use of the cylinder, it should be fixed with an appropriate support. Maintain 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 fallen to a point where the indicator on the valve is within the yellow field.
• When a small amount of gas remains in the cylinder, the cylinder valve should be closed. It is essential that a small amount of pressure remains in the cylinder to prevent the entry of contaminants. Keep the filled and empty containers separate.
• After use, the cylinder valve should be closed with the hand. Depressurize the regulator or connection.

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