Ninoxan 50%/50% medicinal compressed gas

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

NINOXAN 50%/50% medicinal compressed gas.

Nitrous oxide / Oxygen

Read the entire leaflet carefully before you start using this medicine, because it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, consult your doctor or pharmacist.
• This medicine has been prescribed for you only and must not be given to other people, even if they have the same symptoms as you, because it could harm them.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are adverse effects not listed in this leaflet. See section 4.

Leaflet contents

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

1. What Ninoxan is and what it is used for

Ninoxan contains a prepared mixture of nitrous oxide ("medicinal laughing gas", N2O) and oxygen (medicinal oxygen, O2), 50% of each, and must be used by inhaling the gas mixture.

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 mildly sedative effect. These effects occur due to the action of nitrous oxide on the substances that transmit signals in your nervous system.

The 50% oxygen concentration, approximately double that present in ambient air, ensures a safe oxygen content in the inspired gas.

What Ninoxan is used for:

Ninoxan should be used when a rapidly-acting and rapidly-resolving analgesic effect is desired for mild to moderate pain of limited duration.

Ninoxan produces analgesic effects after a few inhalations, and the analgesic effect diminishes within minutes after discontinuation.

Children:

Ninoxan may be used in children older than 1 month of age.

2. What you need to know before using Ninoxan

Do not use Ninoxan:

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

• Gas-filled cavities or gas bubbles: if, due to illness or any other reason, you suspect there is air in your pleural cavities outside the lungs, or gas bubbles in the blood or any other organ (for example, if you have been diving and may have gas bubbles in the blood (decompression sickness); or if you have received an intraocular gas injection, for example, due to retinal detachment, or similar). These gas bubbles may expand and cause damage.

• Heart disease: if you have heart failure or impaired heart function, since the mild relaxing effect of nitrous oxide on the heart muscle may further deteriorate cardiac function.

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

• Central nervous system injury: if you have increased intracranial pressure, for example, due to a brain tumor or cerebral hemorrhage, nitrous oxide may further increase pressure in the brain, potentially causing harm.

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

• Intestinal distension (ileus or ileus): if you have severe abdominal discomfort; if symptoms suggest ileus, Ninoxan may further increase intestinal dilation.

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

• Reduced 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 or have a history of abusing drugs/medications, because there is an increased risk of developing dependence on nitrous oxide if taken repeatedly. Your doctor will decide whether treatment with Ninoxan is possible in your case.

Consult your doctor before starting to use Ninoxan.

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

• Ear discomfort: For example, ear inflammation, since Ninoxan may increase pressure in the middle ear.

• Vitamin deficiency: if you suspect you have vitamin B12 deficiency or folic acid deficiency, for example, if your intake of vitamin B12 or folic acid has decreased, or if you have a genetic disorder affecting the metabolism of these vitamins, or if you are immunocompromised. The use of nitrous oxide may worsen symptoms caused by vitamin B12 and folic acid deficiency.

Your doctor will decide whether Ninoxan is indicated for use in your case.

Repeated or prolonged use of nitrous oxide may increase the risk of vitamin B12 deficiency, which may lead to damage of the bone marrow or nervous system. Your doctor may perform blood tests before and after treatment to assess the potential consequences of vitamin B12 deficiency.

Children

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

Your doctor will decide whether the use of Ninoxan is appropriate.

Use of Ninoxan with other medicines

Inform your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines.

If you are taking other medicines that affect the brain or brain functions, e.g., benzodiazepines (tranquilizers) or morphine-like medicines, you must inform your doctor. Ninoxan may enhance the effects of these medicines. Ninoxan, when taken together with other sedatives or medicines affecting the central nervous system, increases the risk of side effects.

You should also inform your doctor if you are taking medicines containing methotrexate (e.g., for the treatment of rheumatoid arthritis), bleomycin (cancer treatment), nitrofurantoin and other antibiotics (for treatment of infections), or amiodarone (for treatment of heart diseases). Ninoxan increases the side effects of these medicines.

Pregnancy and breastfeeding:

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

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

If Ninoxan is used close to delivery, your baby should be monitored for possible adverse effects.

Breastfeeding

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

Driving and using machines:

Ninoxan has a sedative effect, which may affect your mental and physical performance. 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 consider you to be fully recovered.

3. How to use Ninoxan

Ninoxan must always be administered in the presence of personnel familiar with this type of medication and equipment. During the period when you are using Ninoxan, both you and the administration of the medication must be monitored to ensure that it is administered safely. After completing treatment, you must remain under supervision by qualified personnel until you have fully recovered.

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

Always follow exactly the administration instructions for this medicine given by your doctor. If in doubt, ask your doctor.

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

Regardless of which mask is used, you should breathe normally, taking regular breaths through the mask. Ideally, you should hold the mask yourself.

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

After stopping Ninoxan use, you should rest and recover until you feel mentally alert again.

Safety measures:

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

Use in children

Ninoxan must 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 gas delivery is controlled by your own breathing and the gas mixture is fixed (containing 50% nitrous oxide and 50% oxygen).

If you breathe faster than normal, thereby receiving more nitrous oxide than during normal breathing, you may feel noticeably drowsy and may lose contact with your surroundings to some extent. In such a case, you must immediately inform medical personnel and discontinue inhalation of Ninoxan.

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

In case of overdose or accidental ingestion, contact the Toxicology Information Service.

Telephone: 91 562 04 20.

4. Possible adverse effects

Like all medicines, Ninoxan may cause adverse effects, although not everyone experiences them.

The following adverse effects have been reported:

Adverse effects and their frequency:

Common (may affect up to 1 in 10 patients):

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

Uncommon (may affect up to 1 in 100 patients):

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

Very rare (may affect up to 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 available data):

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

Reporting of adverse effects

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

You may also report them directly through the national reporting system detailed in Appendix V. By reporting adverse 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 stated on the gas cylinder. The expiry date refers to the last day of the month indicated.

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 must be placed horizontally at a temperature above +10°C for at least 48 hours prior to use.

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

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

Different types of gases must be kept separate from each other. Full and empty gas cylinders must be stored separately.

Do not smoke. Avoid exposure to strong heat.

Gas vapours may cause drowsiness and dizziness.

Keep away from combustible materials.

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

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

Keep the cylinder in an upright position.

Ensure the cylinder has not been subjected to impacts or falls.

Must be stored and transported with valves closed.

6. Contents of the pack and other information

Composition of Ninoxan:

• The active substances are:

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

• Ninoxan contains no other ingredients.

Appearance of the product and contents of the container

Ninoxan is a colourless, odourless gas supplied in a steel or aluminium cylinder equipped with a valve to control gas flow.

Cylinders are identified by specific colour coding (white body with blue and white shoulder, with two horizontal bands, the lower one being blue).

Containers

Aluminium cylinder with integrated valve or standard residual pressure valve (RPV):

• 2-litre cylinder filled to 170 bar, providing 0.56 m³ of gas at atmospheric pressure and 15°C.
• 5-litre cylinder filled to 170 bar, providing 1.4 m³ of gas at atmospheric pressure and 15°C.
• 10-litre cylinder filled to 170 bar, providing 2.8 m³ of gas at atmospheric pressure and 15°C.

Seamless steel cylinder with integrated valve or standard RPV:

• 5-litre cylinder filled to 170 bar, providing 1.4 m³ of gas at atmospheric pressure and 15°C.
• 10-litre cylinder filled to 170 bar, providing 2.8 m³ of gas at atmospheric pressure and 15°C.

Seamless steel cylinder with standard RPV:

• 50-litre cylinder filled to 170 bar, providing 14 m³ of gas at atmospheric pressure and 15°C.

Only certain cylinder sizes may be commercially available.

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 most recent revision of this leaflet: 06/2020

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

This information is intended solely for healthcare professionals:

Safety instructions

Special precautions must be taken when handling nitrous oxide. Nitrous oxide should be administered in accordance with local guidelines.

Repeated administration or exposure to nitrous oxide may lead to addiction. Caution is advised for healthcare professionals with occupational exposure to nitrous oxide.

Ninoxan should only be used in well-ventilated areas equipped with special devices to extract excess gas. By using an extraction system and ensuring adequate ventilation, high ambient concentrations of nitrous oxide in the air can be avoided. High concentrations of nitrous oxide in the air may cause adverse health effects in personnel and individuals near the administration site. National limits exist for nitrous oxide concentrations in the air. These limits must not be exceeded to ensure personnel are not exposed to risks.

Occupational exposure limit values for chemicals are often expressed as: TWA (time-weighted average), which is the average value over a working day, and STEL (short-term exposure limit), which is the average value during a shorter exposure period.

Ninoxan is an unstable mixture below -5°C. Temperatures below this may cause temporary liquefaction of nitrous oxide, resulting in inhalation of an uneven mixture, with excess oxygen at the beginning of administration (a mixture with reduced analgesic effect) and excessive nitrous oxide at the end (a hypoxic mixture) of inhalation.

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

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

When used in emergency service vehicles, cylinders must be protected from cold and securely fastened 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 if there is difficulty opening the valve or connecting the regulator. Never force the valve; use only connection devices and seals compatible with the specific gas mixture and oxidizing gases. Never use a tool to connect a manually-operated pressure/flow regulator, as this may damage the coupling.
• Close the cylinder valve in case of fire or if not in use. Always store and transport cylinders with valves closed, even when empty.
• During use, the cylinder must be secured with an appropriate support. Keep containers in an upright position; however, cylinders should be stored horizontally if it is suspected they have been stored at temperatures below -5°C.
• The gas cylinder should be replaced when the pressure in the cylinder drops to the point where the valve indicator enters the yellow field.
• When only 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 entry of contaminants. Keep full and empty containers separate.
• After use, close the cylinder valve by hand. Depressurize the regulator or connection.

For further details, refer to the Summary of Product Characteristics (SmPC) or contact the supplier.