SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

9% Helium/35% Oxygen/Nitrogen Medical Gas Mixture

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

9% Helium / 35% Oxygen / Nitrogen Medical Gas Mixture is a medicinal gas mixture

of Helium, Oxygen and Nitrogen.

The Oxygen and Nitrogen comply with the relevant European Pharmacopoeia Specifications (1998).

The Helium complies with the British Pharmacopoeia Specification (1988) The mixture specification is as follows:_

Carbon Monoxide	5 vpm
Carbon Dioxide	300 vpm
Moisture	50 vpm

3. PHARMACEUTICAL FORM

Inhalation Gas

4.    CLINICAL PARTICULARS

4.1    Therapeutic indications

9% Helium / 35% Oxygen / Nitrogen Medical Gas Mixture is used for pulmonary physiology.

Indications for 9% Helium / 35% Oxygen / Nitrogen Medical Gas Mixture are dictated by the Clinical Investigator.

Posology and method of administration

9% Helium / 35% Oxygen / Nitrogen Medical Gas Mixture is administered through the lungs by inhalation usually through volumetric metering and absorption analysis devices. It may be administered by means of a tent.

4.3 Contraindications

There are no contraindications for the use of 9% Helium / 35% Oxygen / Nitrogen Medical Gas Mixture in any age group.

The use and dosage of 9% Helium / 35% Oxygen I Nitrogen Medical Gas Mixture is

determined by the respiratory function test being applied.

9% Helium / 35% Oxygen / Nitrogen Medical Gas Mixture should not normally be

used with elderly, chronic bronchitic patients as the Oxygen concentration

exceeds

35%.

4.4 Special warnings and precautions for use

9% Helium/ 35% Oxygen / Nitrogen Medical Gas Mixture will support combustion and smoking should be prohibited with its use.

Where the patient has been exposed to agents which are toxic to the lungs, such as Paraquat, the use of gases containing more than 21% oxygen should be avoided.

9% Helium/ 35% Oxygen / Nitrogen Medical Gas Mixture is non flammable but strongly supports combustion and should not be used near sources of ignition.

Smoking should be prohibited when using 9% Helium/ 35% Oxygen / Nitrogen Medical Gas Mixture.

Under no circumstances should oils or grease be used to lubricate any part of the 9% Helium/ 35% Oxygen / Nitrogen Medical Gas Mixture cylinder or the associated equipment used to deliver the gas to the patient.

Where moisturising creams are required for use with a facemask or in nasal passages, oil based creams should not be used.

Check that hands are clean and free from any oils or grease.

Where alcohol gels are used to control microbiological cross-contamination ensure that all alcohol has evaporated before handling 9% Helium/ 35% Oxygen / Nitrogen Medical Gas Mixture cylinders or equipment.

Care is needed in the handling and use of 9% Helium/ 35% Oxygen /Nitrogen Medical Gas Mixture cylinders.

Interaction with other medicinal products and other forms of interaction

The use of higher levels of oxygen can increase the risk of pulmonary toxicity in patients who have been administered Bleomycin, Amiodarone and Nitrofurantoin or similar antibiotics. In these cases 9% helium/35% Oxygen/ Nitrogen medical gas mixture should be administered with caution and at levels kept as low as possible.

4.6 Pregnancy and lactation

9% Helium / 35% Oxygen / Nitrogen Medical Gas Mixture is not contraindicated in pregnancy and is unlikely to influence lactation.

4.7 Effects on ability to drive and use machines

In normal circumstances, 9% Helium / 35% Oxygen I Nitrogen Medical Gas Mixture does not effect ability to drive or to operate machinery.

4.8 Undesirable effects

High barometric pressures, above 3 bar (g), may produce convulsions due to Oxygen content, if continued for more than a few hours.

4.9 Overdose

None applicable.

5.    PHARMACOLOGICAL PROPERTIES

5.1    Pharmacological properties

The characteristics of Helium are:

•    odourless, colourless gas

•    Molecular weight    4

•    Boiling point    -269°C (at I bar (g)

•    Density    0.169 kg/rn³ (at 15°C)

Helium has no physiological activity and will not support life.

The characteristics of Oxygen are:

•    odourless, colourless gas

•    Molecular weight    32

•    Boiling point    -183.1°C (at 1 bar (g)

•    Density    1.355    kg/rn³ (at    1    5°C)

Oxygen is present in the atmosphere at 21% and is an absolute necessity for life.

The characteristics of Nitrogen are:

•    odourless, colourless gas

•    Molecular weight    28

•    Boiling point    -196°C (at 1 bar (g)

•    Density    1.185    kg/rn³ (at    15°C)

Nitrogen is a non-toxic inert gas. It has no physiological activity and will not support life.

5.2 Pharmacokinetic properties

Helium has a low co-efficient of solubility and high rate of diffusion compared with nitrogen. It is completely inert and non-toxic. When Helium replaces the Nitrogen in air, the specific gravity of the resultant Helium mixture will flow through bronchi more easily than air. In patients with respiratory obstruction, therefore, more Oxygen may be presented to the alveolus for the same ventilatory effort. The absorption of Helium from alveoli is very slow. Inhalation of Helium may be used to prevent atelectasis.

The uptake of Oxygen by the blood in the lungs and discharge to the tissues is determined by the Oxygen dissociation curve. The characteristic sigmoid shape ensures that, at tensions between 40 and 15 mm Hg, the Oxygen carried in the blood form the lungs can be readily given up to the tissues.

The uptake from the lungs is rapid because blood flow through the capillaries, where exchange takes place, occurs in about 0.5 seconds. The uptake of Oxygen is favoured by the simultaneous loss of Carbon Dioxide which is then excreted in the expired air. Conversely the entry of carbon dioxide into the blood from the tissues facilitates Oxygen transfer to the cells.

At rest, mixed venous blood returning to the lungs contains 13-14 ml of Oxygen per 100 ml, but with severe exercise, the oxygen content may fall to 3-4 ml. In very active tissue, almost complete extraction occurs.

Nitrogen is soluble in fat but saturates slowly. Under pressure, Nitrogen will form bubbles in tissues and blood.

5.3 Preclinical safety data

None stated

6. PHARMACEUTICAL PARTICULARS 6.1    List of excipients

None.

6.2 Incompatibilities

The constituent gases of 9% Helium / 35% Oxygen / Nitrogen Medical Gas Mixture are chemically inactive and will not normally react with other compounds at normal temperatures.

However, the Medical Oxygen component of 9% Helium / 35% Oxygen / Nitrogen Medical Gas Mixture strongly supports combustion and will cause substances to burn, including some materials that will not normally burn in air. It is highly dangerous in the presence of oils, greases, tarry substances and many plastics due to the risk of spontaneous combustion in the presence of Medical Oxygen in relatively high concentrations.

6.3 Shelf life

36 months

6.4 Special precautions for storage

9% Helium / 35% Oxygen / Nitrogen Medical Gas Mixture cylinders should

be stored as follows:

•    Cylinders should be stored under cover, preferably inside, kept dry and clean and not subjected to extremes of heat or cold, away from stocks of material.

•    Cylinders should not be stored near stocks of combustible materials or near sources of heat.

•    Medical cylinders should be stored separately from industrial and other non-medical cylinders.

•    Full and empty cylinders should be stored separately.

•    Full cylinders should be used in strict rotation.

•    Segregate medical cylinders containing different gases within the store.

•    Warning notices prohibiting smoking and naked lights must be posted clearly.

•    Emergency services should be advised of the location of the cylinder store.

6.5 Nature and contents of containers

9% Helium 135% Oxygen I Nitrogen Medical Gas Mixture Cylinder and Valve Details

All cylinders used for the storage of 9% Helium I 35% Oxygen I Nitrogen Medical Gas Mixture are manufactured from aluminium with a designed working pressure of at least 150 bar (g).

A summary of 9% Helium / 35% Oxygen I Nitrogen Medical Gas Mixture cylinders, their size and construction, type of valve fitted and valve outlet connection is detailed below:

□ Cylind er Size	Gas Content (litres)	Cylinder Construction	Valve Outlet	Valve Constructio n
AV	1500	Aluminium	BS 341 No.4 / Side Outlet	Brass
L	6000	Aluminium	BS 341 No.4 / Side Outlet	Brass

The cylinder valves are constructed from high tensile brass with a steel spindle fitted with a Nylon 66 insert.

6.6 Instructions for use and handling

All personnel handling 9% Helium / 35% Oxygen / Nitrogen Medical Gas Mixture cylinders should have adequate knowledge of the properties of the gas, precautions to be taken, actions in the event of an emergency and the correct operating procedures for their installations.

Preparation for Use

Prior to use ensure that:

•    An appropriate medical gas regulator is used with the cylinder, suitable for use with 9% Helium / 35% Oxygen / Nitrogen Medical Gas Mixture.

•    The connecting face of the regulator is clean and the sealing washer fitted is in good condition.

•    The cylinder valve is opened slowly.

•    The cylinder valves and any associated equipment is not lubricated and kept free form oil and grease.

Leaks

Care should be taken to ensure there are no leaks between the regulator

connection and the cylinder valve.

The following precautions should be followed:

•    Should leaks occur this will usually be evident by a hissing noise.

•    Leaks can be found by brushing the suspected area with an approved leak test solution such as 1% Teepol HB7 solution.

•    Sealing or jointing compounds must never be used to cure a leak.

•    Should a leak occur between the valve outlet and the detachable regulator, depressurise and remove the regulator and fit a new ‘O’ ring. Reconnect the regulator to the valve with moderate force only. If the leak persists fit a replacement regulator.

•    Never use excessive force when connecting equipment to cylinders.

Use of Cylinders

When cylinders are in use ensure that they are:

•    Handled with care and knocked violently or allowed to fall.

•    Only to be moved with appropriate size and type of trolley or handling device.

•    Firmly secured to a suitable cylinder support.

•    Only to be used for medicinal purposes

•    Not used in the vicinity of persons smoking or near naked lights.

After use the cylinder valves should be closed using moderate force only and

the pressure in the regulator released.

When the cylinder is empty ensure that:

•    The cylinder valve is closed.

•    The valve outlet cap, where fitted, is replaced.

•    The empty cylinder is immediately returned to the cylinder store for return to BOC.

7    MARKETING AUTHORISATION HOLDER

BOC Limited.

The Priestley Centre

10 Priestley Road

The Surrey Research Park

GUILDFORD

Surrey

GU2 5XY

MARKETING AUTHORISATION NUMBER

PL 00735/5015R

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date First Granted:	01/09/1972
Date of Renewal:	27/03/1996

10 DATE OF REVISION OF THE TEXT

23/04/2013