Heliox²⁸

MIMS Revision Date: 01 January 2021

1 Name of Medicine

Helium and oxygen.

2 Qualitative and Quantitative Composition

Heliox28 is a homogenous gas mixture of oxygen 28% v/v and helium 72% v/v.
Oxygen is the active ingredient.
Specification. The specifications for each of the main components are presented separately.
Oxygen. Complies with the requirements of the current European Pharmacopoeia monograph for Oxygen.
Oxygen: 99.5% v/v minimum.
Carbon dioxide: 300 ppm v/v maximum.
Carbon monoxide: 5 ppm v/v maximum.
Water (vapour): 67 ppm v/v maximum.
Helium. Complies with BOC specification for Medical Helium.
Helium: 99.99% v/v minimum.
Hydrocarbons as Methane: 1 ppm v/v maximum.
Carbon monoxide: 5 ppm v/v maximum.
Water (vapour): 67 ppm v/v maximum.
There are no excipients.

3 Pharmaceutical Form

Compressed medical gas mixture (for medicinal use only).
Oxygen is a colourless, odourless and tasteless gas. Helium is a colourless, odourless, non-flammable gas.

4 Clinical Particulars

4.1 Therapeutic Indications

Heliox28 is indicated in treatment of hypoxia associated with airway obstruction.

4.2 Dose and Method of Administration

Routes of administration. Heliox28 is administered by inhalation through the lungs. Heliox28 should only be administered by medical personnel trained in the appropriate techniques and in an adequate environment.
The method of administration is to supply the medical gas mixture directly from the outlet of the medical cylinder valve, via an appropriate flexible hose connected to either a face mask or cannula, a demand valve with face mask or cannula attached, a nebuliser or inhaler with face mask attached or a ventilator.
Cylinders should only be used in conjunction with special Heliox28 gas pressure regulators and demand valves.
Safety of long term administration of Heliox28 has not been studied.

4.3 Contraindications

Heliox28 should not be used where its high diffusivity might exacerbate conditions, such as with artificial, traumatic or spontaneous pneumothorax or sub-cutaneous emphysema.

4.4 Special Warnings and Precautions for Use

General. Oxygen saturation levels should be monitored in patients receiving Heliox28. If oxygen saturation is not adequately maintained, additional oxygen may be mixed with Heliox28. However caution should be exercised to avoid oxygen toxicity (e.g. retinopathy in premature neonates treated with prolonged hyperoxygenation).
Caution should also be exercised in patients with chronic obstructive pulmonary disease (COPD), in whom respiration may be dependant upon hypoxic drive. In hypercarbic COPD patients, arterial blood gases should be monitored to detect any increase in acidosis.
Smoking is prohibited when the product is in use and no naked flames should be allowed.
Check the following before use. Cylinders should be stored upright below 45°C in a dry well ventilated area.
Heliox28 is non-flammable but strongly supports combustion (including some materials which do not normally burn in air). It is highly dangerous when Heliox28 comes into contact with oils, greases and tarry substances due to the risk of spontaneous combustion.
Dispensing equipment connection matches cylinder valve pin index outlet and demand valve is operational.
Cylinder pressure may be used as an indicator of the quantity of the gas remaining in the cylinder.
Use of gas cylinders. Cylinders should be kept out of the reach of children.
Care is needed in the handling and use of Heliox28 gas cylinders. Heliox28 is stored in high pressure gas cylinders under pressure at ambient temperature.
Additional information is contained in the Material Safety Data Sheet for Heliox28 from the sponsor.
Use in the elderly. No data available.
Paediatric use. No data available.
Effects on laboratory tests. There are no known significant effects on laboratory tests after exposure to Heliox28.

4.5 Interactions with Other Medicines and Other Forms of Interactions

There are no adequate human or animal studies reports on interaction of helium/ oxygen mixtures with other drugs available.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility. There are no adequate human or animal studies addressing the effect of helium/ oxygen gas mixtures on fertility or reproductive performance.
Use in pregnancy. No relevant epidemiological data or adequate and well-controlled clinical data on exposed pregnancies are available for helium/ oxygen gas mixtures.
No data from animal studies using mammalian species that would enable assignment of a 'Use in pregnancy' classification are available.
Studies in chicken eggs exposed continuously to a 21% oxygen/79% helium gas environment from lay up to 4 weeks post-hatch have revealed impaired hatchability, increased embryonic mortality and decreased embryonic weight.
Use of Heliox28 is not recommended during pregnancy, unless clearly necessary.
Use in lactation. There are no adequate human or animal studies addressing the effect of helium/ oxygen gas mixtures on lactation.

4.7 Effects on Ability to Drive and Use Machines

There is no evidence on the effects of Heliox28 on the ability to drive and use machinery.

4.8 Adverse Effects (Undesirable Effects)

Increased vocal pitch and voice distortion due to helium.
Inhalation of Heliox28 has the potential to cause drying of mucous membranes, including the drying out of bronchial secretions and subsequent atelectasis.
Prolonged inhalation of helium has the potential to cause a reduction in body temperature.
The use of helium/oxygen has been observed to cause hypoxia in neonates with bronchopulmonary dysplasia and subglottic stenosis.
Reporting suspected adverse effects. Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.

4.9 Overdose

None applicable.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action. Oxygen is a naturally occurring element which is essential for metabolism and homeostasis in man. It comprises approximately 21% of atmospheric air.
Helium is a biologically inert element which is approximately seven times less dense than nitrogen.
The oxygen/ helium mixture therefore has a lower density that air and, in the presence of airway obstruction, is more likely to be associated with laminar, rather than turbulent, flow. This results in improved oxygen delivery to the alveoli.
Clinical trials. Multiple clinical trials of oxygen/helium mixtures in the management of conditions associated with airway obstruction have been reported in the published literature. These studies have been predominantly conducted in patients with chronic obstructive pulmonary disease (COPD) or asthma.
In controlled trials in these conditions, the use of helium/ oxygen has been associated with improvements in peak expiratory flow rate (PEFR), reductions in PaCO₂ and work of breathing, reversal of acidosis and decreased dyspnoea.

5.2 Pharmacokinetic Properties

Oxygen is absorbed into the systemic circulation and distributed throughout the body.
Helium has low solubility in human tissues at atmospheric pressure and is therefore not significantly absorbed systemically.

5.3 Preclinical Safety Data

Genotoxicity. No data available.
Carcinogenicity. Long-term animal studies on carcinogenicity are not available for helium/ oxygen gas mixtures.
A 50 or 100 atmosphere helium/0.21 atmosphere oxygen gas mixture was not mutagenic in TA98 and TA100 strains of Salmonella typhimurium.

6 Pharmaceutical Particulars

6.1 List of Excipients

None.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

Not applicable.

6.4 Special Precautions for Storage

The normal precautions required in the storage and use of medical gas cylinders are applicable. Please refer to Commonwealth, State and Territory Dangerous Goods legislation and the appropriate Australian Standards i.e. AS 4332. Cylinders should be stored away from sources of ignition, poisons, flammable or combustible materials. They should preferably be stored upright, in a secure area, below 45°C, in a dry well ventilated area constructed of non-combustible material with a firm, level floor (preferably concrete) away from heavy traffic and emergency exits.

6.5 Nature and Contents of Container

Compressed medical gas (for medicinal use only) supplied in cylinders in accordance with AS2030 and pin index valve in accordance with AS2472.
Cylinder colour. Shoulder: brown and white quadrants.
Body: neutral with white plastic sleeve with Heliox28 and Helium/Oxygen artwork.
Cylinder valve outlet. Regulated to 400 kPa, either AS2896 sleeve outlet (300 lpm) or barbed tail (0 to 15 lpm).
Cylinder size (nominal water capacity, liters). CD (2.4 L); ED (23.8 L).
Cylinder size (gas volume, liters at 15°C; 1 At). CD (510 L); ED (3500 L).

6.6 Special Precautions for Disposal

Please consult the Material Safety Data Sheet for helium/ oxygen gas mixture from the sponsor.

6.7 Physicochemical Properties

Chemical structure. Oxygen has a molecular structure of O=O.
Helium symbol is He.
CAS number. Oxygen - 7782-44-7.
Helium - 7440-59-7.
Physical data. Molecular/ Atomic weight: O₂ 32.00, He 4.0026.
Physical state in the cylinder: High pressure gas at ambient temperature.
Combustion characteristics: Non flammable but strongly supports combustion.
Chemical characteristics. Oxygen is an oxidising substance which will support combustion of materials which may not normally burn in air. Helium is an inert gas with low chemical activity. Helium is less dense than any other known gas except hydrogen and is about one seventh as dense as air.

7 Medicine Schedule (Poisons Standard)

Not scheduled.

Date of First Approval

21 August 2003

Date of Revision

09 November 2020

Summary Table of Changes