Oxynox
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Oxynox.
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
oxygen 50% v/v
nitrous oxide 50% v/v
3. PHARMACEUTICAL FORM
Inhalation gas
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Oxynox is used exclusively for the relief of pain. Common examples of the
use of Oxynox are:
• Acute trauma
• Short-term relief in dental work
• Short-term relief for procedures inevitably involving pain, such as wound and bum dressing, wound debridement and suturing.
• Normal labour
• Acute surgical or medical conditions in which the pain is relieved, only to return on cessation of the analgesia so allowing an unfettered assessment to be made.
4.2 Posology and method of administration
Oxynox is administered through a face mask. The mask is connected to an Oxynox supply through a demand valve system. The valve is operated by the act of inhalation of the patient and closes down when the patient ceases to inhale.
In nearly all cases, Oxynox is self-administered, but it may be administered by attendant medical personnel. Since pain is usually relieved by a concentration of 25% nitrous oxide, continued inhalation does not occur. However, should inhalation continue, light anaesthesia supervenes and the mask drops away as the patient relaxes, or is removed if administration has been by attendant personnel.
There are no contra-indications to the use of Oxynox in any age group.
Doses may be self-regulating in nearly all cases by the use of a face mask connected through a demand valve to the Oxynox cylinder.
Oxynox may be administered by personnel trained in its use (obstetric units, accident units and accident ambulances).
There is no risk of overdose with Oxynox in medical use.
Oxynox should not be used for more than a total of 24 hours, or more frequently than every 4 days, without close clinical supervision and haematological monitoring (see sections 4.4 and 4.8)
4.3 Contraindications
Oxynox should not be used in any condition where air is entrapped within the body and where its expansion might be dangerous, e.g:
• Artificial, traumatic or spontaneous pneumothorax.
• Air embolism
• Decompression sickness
• Following a recent dive
• Following air encephalography
• Severe bullous emphysema
• Use during myringoplasty
• Gross abdominal distension
4.4 Special warnings and precautions for use
The nitrous oxide constituent of Oxynox causes inactivation of vitamin B12, which is a co-factor of methionine synthase. Folate metabolism is consequently interfered with and DNA synthesis is impaired following prolonged nitrous oxide administration. Prolonged or frequent use of nitrous oxide may result in megaloblastic marrow changes, myeloneuropathy and sub acute combined degeneration of the spinal cord
Oxynox should not be used for more than a total of 24 hours; or more frequently than every 4 days, without close clinical supervision and haematological monitoring. Specialist advice should be sought from a haematologist in such cases. Haematological assessment should include an assessment for megaloblastic change in red cells and hypersegmentation of neutrophils. Neurological toxicity can occur without anaemia or macrocytosis and with B12levels in the normal range.
In patients with undiagnosed subclinical deficiency of vitamin B12, neurological toxicity has occurred after single exposures to nitrous oxide during general anaesthesia.
Thorough ventilation or scavenging of waste gases should reduce operating theatre and equivalent treatment room levels of ambient nitrous oxide to a level below 200 ppm. Oxynox is non flammable but strongly supports combustion (including some materials which do not normally burn in the air). It is highly dangerous when in contact with oils, greases, tarry substances and many plastics.
Do not smoke when using Oxynox.
Care is needed in the handling and use of Oxynox gas cylinders.
4.5 Interactions with other Medicinal products and other forms of interaction
The nitrous oxide constituent of Oxynox inactivates vitamin B12 and may potentiate the therapeutic effects of methotrexate.
4.6 Pregnancy and lactation
Mild skeletal teratogenic changes have been observed in pregnant rat embryos when the dam has been exposed to high concentrations of nitrous oxide during the period of organogenesis.
However, no increased incidence of foetal malformation has been discovered in 8 epidemiological studies and case reports in human beings.
There is no published material which shows that nitrous oxide is toxic to the human foetus or during breast feeding. Therefore, there is no absolute contra-indication to its use in the first 16 weeks of pregnancy, during breast feeding or from occupational exposure during pregnancy.
4.7 Effects on ability to drive and use machines
A slight but quantifiable impairment of driving ability has been found up to 30 minutes after inhalation of 50% nitrous oxide/50% oxygen for 15 minutes. Driving, use of machinery, and other psychomotor activities should not be undertaken for 12 hours following use of Oxynox.
4.8 Undesirable effects
Events such as euphoria, disorientation, sedation, nausea, vomiting, dizziness and generalised tingling are commonly described. These events are generally minor and rapidly reversible.
Prolonged or frequent use of nitrous oxide, including heavy occupational exposure and addiction, may result in megaloblastic anaemia. Agranulocytosis has been reported following prolonged nitrous oxide administration (see section 4.4)
Myeloneuropathy and sub acute combined degeneration have also been reported following prolonged or frequent use. However in patients with undiagnosed
subclinical deficiency of vitamin B12, neurological toxicity has occurred after a single exposure to nitrous oxide for anaesthesia (see section 4.4)
Addiction may occur.
Nitrous oxide passes into all gas containing spaces in the body faster than nitrogen passes- out. Prolonged exposure may result in bowel distension, middle ear damage and rupture of ear drums.
4.9 Overdose
Inappropriate, unwitting or deliberate inhalation of Oxynox will ultimately result in unconsciousness, passing through stages of increasing lightheadedness and intoxication.
Treatment should be: removal to fresh air, mouth to mouth resuscitation and if necessary, the use of an oxygen resuscitator.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
The characteristics of oxygen are:
• colourless, odourless gas
• molecular weight 32.00
• boiling point -183.1 °C (at 1 bar)
• density 1.355 kg/m3 (at 15°C)
Oxygen is present in the atmosphere at 21% and is an absolute necessity for life.
At the concentrations of Oxynox, oxygen has no discernible pharmaceutical effect other than the beneficial effects of an oxygen enriched mixture in certain cases.
NITROUS OXIDE
The characteristics of Nitrous oxide are:
• sweet smelling, colourless gas
• molecular weight 44.00
• boiling point -88.6°C (at 1 bar)
density 1.875 kg/in3 (at 15°C)
Nitrous oxide is not very soluble in water but is fifteen times more soluble than oxygen. Water dissolves Nitrous Oxide, taking 100%, and blood plasma 45 vol%.
Nitrous oxide is eliminated from the body mostly by the lungs.
Nitrous oxide is a potent analgesic and a weak anaesthetic. Induction with Nitrous oxide is relatively rapid, but a concentration of about 70% is needed to produce unconsciousness. Endorphins are probably involved in the analgesic effect; a concentration of 25% Nitrous oxide is usually adequate to provide a marked reduction in pain.
5.2 Pharmacokinetic properties
There are no essential observations about the pharmacokinetics of oxygen at this concentration.
Nitrous oxide is a low potency inhalation anaesthetic and high potency analgesic.
At a constant inspired concentration the rise time of alveolar concentrations is faster than that of any other anaesthetic agent. The elimination of Nitrous Oxide equally is faster than that of any other anaesthetic. This characteristic is especially valuable in analgesia for short-term pain relief.
The blood/gas partition co-efficient of Nitrous Oxide at 37°C is 0.46 compared with that of nitrogen of 0.015 causing Nitrous Oxide to expand into the internal gas spaces.
5.3 Preclinical safety data
All relevant information for the prescriber is provided elsewhere in the Summary of Product Characteristics.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
None.
6.2 Incompatibilities
Oxynox is chemically inactive and will not react with other compounds at normal temperatures.
Shelf life
6.3
36 months.
6.4 Special precautions for storage
Oxynox cylinders should be stored
• Under cover
• Away from stocks of materials and not subjected to extremes of heat
• Stored separately from industrial and other non-medical cylinders
• Full and empty cylinders stored separately.
6.5 Nature and contents of container
The container is a cylinder of high-strength chromium-molybdenum steel, designed for a
charge pressure of up to 300bar. The actual charging pressure is 137bar. It is fitted with a
brass pin-index valve conforming to the current BSEN 850: 1997 standard pin Figure 8.
The sizes and volume of content as uncompressed gas are as tabulated:
|
water capacity of cylinder (litres) |
volume of gas at 15 °C and atmospheric pressure (litres) |
Valve Type |
|
2 |
428 |
Pin Index |
|
2.5 |
536 |
Pin Index |
|
5 |
1,071 |
Pin Index |
|
9.43 |
2,020 |
Pin Index |
|
10 |
2,140 |
Pin Index |
|
20 |
4,280 |
Pin Index |
|
23.6 |
5,056 |
Pin Index |
|
30 |
6,420 |
Pin Index |
|
47 |
10,100 |
Pin Index |
6.6 Special precautions for disposal
Use in accordance with the doctor’s instructions.
Cylinders must be used in the vertical position with the valve uppermost so as to avoid the discharge of liquid contents. Avoid rapid opening of the valve as this could lead to reliquification of the discharged gas. In its liquid form the substance in contact with the skin can cause cold burns.
Oxynox supports combustion more vigorously than does air.
There is danger of spontaneous combustion when organic substances come into contact with the high pressure gas. This applies to substances such as grease, oil and some plastics.
If storage has taken place below 0°C then the contents of the cylinder must be re-mixed, using one of the following methods:
store the cylinder horizontally for 24 hours at above 10°C; or mix the contents by fully inverting the cylinder three times, after warming it at above 10°C for at least two hours.
GENERAL
1) All personnel handling gas cylinders or being responsible for pipeline gas supplies should have adequate knowledge of the properties of the gas, precautions to be taken, actions in the event of any emergency and the correct operating procedures for their installation.
2) If you own your own cylinders you must be aware of, and discharge your statutory obligations with regard to maintenance and testing.
3) Ensure that when cylinders are collected the driver has been properly instructed in the method of handling cylinders and in dealing with any emergency.
STORAGE OF CYLINDERS
kept dry and materials or near
1) Cylinders should be stored under cover, preferably inside, clean and not subjected to extremes of heat or cold.
2) Cylinders should not be stored near stocks of combustible sources of heat.
3) Warning notices prohibiting smoking and naked lights must be posted clearly.
4) Emergency services should be advised of the location of the cylinder store.
5) Medical cylinders containing different gases should be segregated within the store.
6) Full and empty cylinders should be stored separately. Full cylinders should be used in strict rotation.
7) Medical cylinders should be stored separately from industrial and other non-medical cylinders.
8) Cylinders must not be repainted, have any markings obscured or labels removed.
9) F size cylinders and larger should be stored vertically. E size cylinders and smaller should be stored horizontally.
10) Precautions should be taken to protect cylinders from theft. PREPARATION FOR USE
1) Cylinder valves should be opened momentarily prior to use to blow any grit or foreign matter out of the outlet.
2) Ensure that the connecting face on the yoke, manifold or regulator is clean and the sealing washer or ‘0’ ring where fitted is in good condition.
3) Cylinder valves must be opened slowly.
4) Only the appropriate regulator should be used for the particular gas concerned.
5) Pipelines for medical gases should be installed in accordance with the conditions set out in HTM 2022.
6) Cylinder valves and any associated equipment must never be lubricated and must be kept free from oil and grease.
LEAKS
1) Should leaks occur this will usually be evident by a hissing noise.
2) Leaks can be found by brushing the suspected area with an approved leak test solution such as 1% Teepol HB7 solution.
3) The gland packing around the valve spindle may become loose and can be cured by tightening the gland nut clockwise. Do not overtighten.
4) Sealing or joining compounds must never be used to cure a leak.
5) Never use excessive force when connecting equipment to cylinders.
USE OF CYLINDERS
1) Cylinders should be handled with care and not knocked violently or allowed to fall.
2) Cylinders should only be moved with the appropriate size and type of trolley.
3) When in use cylinders should be firmly secured to a suitable cylinder support.
4) Cylinders containing liquefiable gas must always be used vertically with the valve uppermost.
5) Medical gases must only be used for medicinal purposes.
6) Smoking and naked lights must not be allowed within the vicinity of cylinders or pipeline outlets.
7) After use cylinder valves should be closed using moderate force only and the pressure in the regulator or tailpipe released.
8) When empty the cylinder valve must be closed.
9) Ensure the plastic valve cap is refitted to bullnose valves/outlets.
10) Immediately return empty cylinders to the empty cylinder store for return to Air Products.
7 MARKETING AUTHORISATION HOLDER
Air Products plc Weston Road Crewe Cheshire CW1 6BT
8. MARKETING AUTHORISATION NUMBER
PL 06183/0013
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
15/12/2008
10 DATE OF REVISION OF THE TEXT
03/02/2009