Package leaflet: Information for the user

Protoxan 50% / 50%, medicinal gas, compressed

nitrous oxide / oxygen

Read all of this leaflet carefully before you start using this medicine because it contains

important information for you.

• Keep this leaflet. You may need to read it again.

• If you have any further questions, ask your doctor or pharmacist.

• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.

• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet

1. What Protoxan is and what it is used for

2. What you need to know before you use Protoxan

3. How to use Protoxan

4. Possible side effects

6. Contents of the pack and other information

Protoxan contains a ready mixture of nitrous oxide (medicinal “laughing gas”, N₂O) and oxygen (medicinal oxygen, O₂), 50% of each, and should be used by breathing in the gas mixture.

The effects of Protoxan:

Nitrous oxide constitutes 50% of the gas mixture. Nitrous oxide has a painkilling effect, reduces the sensation of pain and raises the pain threshold. Nitrous oxide also has a relaxing and slightly calming effect. These effects are produced by the effects of nitrous oxide on signal substances in your nervous system.

The 50% concentration of oxygen, around double that in the ambient air, guarantees a safe oxygen content in the inspired gas.

What Protoxan is used for

Protoxan should be used when painkilling effects, of rapid onset and rapid resolution are desired and when the treated state of pain is of mild to moderate intensity and of limited duration.

Protoxan produces an analgesic effect after few breaths and the painkilling effects subside within minutes after use is ceased.

Children

Protoxan can be used in children older than 1 month.

2. What you need to know before you use Protoxan

Do not use Protoxan:

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

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

• Heart disease: if you have heart failure or severely impaired heart function, since the slightly relaxing effect of nitrous oxide on the heart muscle can further impair cardiac function.

• Following cardiopulmonary bypass with heart lung machine or coronary by-pass without heart lung machine.

• Central nervous system injury: if you have increased pressure in the brain, e.g., as a result of a tumour or bleeding in the brain. Nitrous oxide can further increase the pressure in the brain with potential risk of harm.

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

• Dilatation of the gut (Ileus): if you have severe abdominal discomfort or other symptoms that may indicate ileus since Protoxan can further increase dilatation of the gut.

• If you have a facial injury the use of masks may present difficulties or risks.

• Decreased level of consciousness or impaired ability to cooperate and follow instructions because of the risk that further sedation from the nitrous oxide may affect natural protective reflexes.

Warnings and precautions

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

Your doctor will decide whether Protoxan is suitable for use.

Children

Protoxan shall not be used in children younger than 1 month.

Your doctor will decide whether it is appropriate to use Protoxan.

Other medicines and Protoxan

Tell your doctor or healthcare professional 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, e.g. benzodiazepines (tranquilizers) or morphine-like medicines, you should tell your doctor. Protoxan may increase the effects of these medicines. The use ofProtoxan together with other sedatives or medicines that affect the central nervous system increases the risk of side effects.

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

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or healthcare professional for advice before using this medicine.

Pregnancy

You should avoid the use of Protoxan during the first 6 months of pregnancy because of potential risk to the foetus. Protoxan can be applied during the last three months of pregnancy and during delivery, but if used close to delivery; your baby should be observed in order to detect any adverse effects.

Breast-feeding

Protoxan can be used during breast-feeding period, however should not be used during breast-feeding itself.

Driving and using machines

Protoxan has a sedative effect, and it can affect how your mind and body works. For safety reasons, you should therefore avoid driving, operating machinery or performing complicated tasks until you have fully recovered. Check with your healthcare professional when he/she thinks that you are fully recovered.

3. How to use Protoxan

Protoxan is always given under the supervision and presence of healthcare professionals familiar with this type of medicine and equipment. Throughout the period during which you use Protoxan you, and the administration of the medicine, will be monitored to ensure that it is administered safely. After finishing treatment, you should be monitored by competent personnel until you have recovered.

Always use Protoxan exactly as your doctor has instructed you. He/She should explain how to use Protoxan, how it works and what effects result from its use. Check with your doctor if you are not sure.

Protoxan is usually inhaled through a face mask attached to a special valve, which means you have full control of the flow of gas by virtue of your own breathing. The valve is only open during inspiration. Protoxan can also be administered via a so-called nasal mask.

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

You should start using Protoxan shortly before the painkilling effect is required and continue through the painful process. The effect of Protoxan wears of within a few minutes after discontinuation of the inhalation.

After you stop using Protoxan you must rest and recover until you feel you have recovered mentally.

Safety precautions:

Use in children

Protoxan shall not be used in children younger than 1 month.

If you use more Protoxan than you should

It is unlikely that you receive too much gas, since the gas is inhaled and controlled by your own breaths and the gas mixture is fixed (with 50% nitrous oxide and 50% oxygen).

If you breathe faster than normal, thus receiving more nitrous oxide than you would with normal breathing, you may feel noticeably tired and out of touch with your surroundings. In this case, you must immediately inform the healthcare professionals and stop inhaling Protoxan.

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

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

The following side effects have been reported:

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

• Dizziness, vertigo (a feeling of dizziness or “spinning”), feeling faint.

• Light headaches.

• Euphoria.

• Nausea and vomiting.

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

• Severe tiredness.

• Feeling of pressure in the middle ear, if Protoxan is used for prolonged period.

• Abdominal bloating, because Protoxan slowly increases the volume of gas in the intestines.

Very rare (may affect up to 1 in 10,000 people)

Not known (frequency cannot be estimated from the available data):

• Effects on bone marrow, which can cause anaemia. Low levels of white blood cells.

• Psychiatric effects, including psychosis, confusion and anxiety.

• Headache.

• Respiratory depression.

Reporting of side effects

If you get any side effects, talk to your doctor.This includes any side effects 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. How to store Protoxan

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 after EXP. The expiry date refers to the last day of that month.

Do not store below -5 °C.

The mixture is unstable below -5 ºC. On suspicion that Protoxan has been stored at temperatures below -5 ºC, the cylinders should be stored in a horizontal position at a temperature above 10 ºC for at least 48 hours before use.

When it is used in emergency service vehicles, the cylinders must be protected from the cold and firmly secured, inside and outside of the vehicles.

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

Different gas types must be separated from each other. Full and empty gas cylinders must be stored separately.

No smoking. Must not be exposed to strong heat.

Vapour may cause drowsiness and dizziness.

Keep away from combustible material.

If at risk of fire, move to a safe place.

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

Keep in upright position.

Make sure the cylinder is not knocked over or dropped.

Store and transport with valves closed.

6. Contents of the pack and other information

What Protoxan contains:

• The active substances are: Nitrous oxide 50% = medicinal laughing gas (chemical formula: N₂O) and Oxygen 50% = medicinal oxygen (chemical formula: O₂)

• Protoxan does not contain any other ingredient

What Protoxan looks like and contents of the pack

Protoxan is a colourless, odourless gas, provided in a gas cylinder of steel or aluminium with a valve to control the flow of gas.

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

Pack sizes:

Aluminium cylinder with integrated valve or normal PRV valve:

2-litres filled at 170 bar gives 0.56 m3 gas at atmospheric pressure and 15 °C.

5-litres filled at 170 bar gives 1.4 m³gas at atmospheric pressure and 15 °C.

10-litres filled at 170 bar gives 2.8 m³gas at atmospheric pressure and 15 °C.

Seamless steel gas cylinder with integrated valve or normal PRV valve:

5-litres filled at 170 bar gives 1.4 m³gas at atmospheric pressure and 15 °C.

10-litres filled at 170 bar gives 2.8 m³gas at atmospheric pressure and 15 °C.

Seamless steel gas cylinder with normal PRV valve:

50-litres filled at 170 bar gives 14 m³gas at atmospheric pressure and 15°C.

Not all pack sizes may be marketed.

Marketing Authorisation Holder:

To be completed nationally

Manufacturer:

Praxair España, S.L.U

Ctra. Villaverde – Vallecas Km 4,8

28053 Madrid

Spain

Praxair NV

Nijverheidsstraat 4

Westerlo, 2260

Belgium

This leaflet was last revised in 2016-08-18

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The following information is intended for healthcare professionals only:

Safety Instructions

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

Protoxan should only be used in areas that are well ventilated and where there is special equipment to remove the excess of gas. Using an extractor system and ensuring good ventilation, high atmospheric concentrations of nitrous oxide in ambient air are avoided.

High concentrations of nitrous oxide in the ambient air can cause negative health effects in personnel or other people close to the place of administration. There are nationally set hygienic limit valuesfor the concentration of nitrous oxide in the ambient air. These should not be exceeded, in order to ensure that the personnel are not exposed to risks. The so-called "Threshold Limit Values TLV" of occupational exposure to chemicals are often expressed as TWA (time weight average), which is the average value over a working day, and STEL (short-term exposure Limit), which is the average value over a shorter exposure.

Protoxan is an unstable mixture below -5 °C. Lower temperatures can cause a temporary liquefaction of the nitrous oxide, which would lead to a uneven mix, with too much oxygen at the beginning of the administration (mixture with less analgesic effect) and too much nitrous oxide at the end (hypoxic mixture) of the inhalation.

On suspicion that Protoxan has been stored at temperatures below -5 ºC, the cylinders should be stored in a horizontal position at a temperature above 10 ºC for at least 48 hours before use. It is recommended that the cylinder is shaken by inverting it completely at least three times to ensure homogenization before use.

Keep the cylinder in a storage area reserved for medical gases. Different gas types must be separated from each other. Full and empty gas cylinders must be stored separately.

When it is used in emergency service vehicles, the cylinders must be protected from the cold and firmly secured, inside and outside of the vehicles.

Other instructions:

• Keep away from combustible materials. No smoking.

• Open the valve slowly and carefully. Never use oil or grease, even if the cylinder valve difficult to open or if the regulator is difficult to connect. Never force the valve, use only connection devices and seals compatible with the specific mixture of gas and for oxidizing gases. Never use a tool to connect a pressure/flow regulator that is intended to be connected manually, as this can damage the coupling.

• Close the cylinder valve in case of fire, or when not in use. Store and transport the cylinders always with the valves closed, even when they are empty.

• When the cylinder is in use it must be fixed in a suitable support. Keep containers upright, however the cylinders should be stored in horizontal position when there is a suspicion that the cylinder has been stored at temperatures below -5 ºC.

• The gas cylinder should be replaced when the pressure in the cylinder has dropped to a point where the indicator on the valve is within the yellow field.

• When a small quantity of gas is left in the gas cylinder, the cylinder valve must be closed. It is important that a small amount of pressure be left in the cylinder to avoid the entrance of contaminants. Keep full and empty cylinders separated.

• After use, the cylinder valve must be closed hand-tight. Depressurize the regulator or connection.

• For more details read the Summary of Product Characteristics (SmPC) or contact the provider.