Nitronox Inhalation Gas
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Nitronox Inhalation Gas
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
Nitronox is used exclusively for the relief of pain. Common examples of the
use of Nitronox are:
• Acute trauma
• Short-term relief in dental work
• Short-term relief for procedures inevitably involving pain, such as wound and burn 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
Nitronox is administered through a face mask or mouthpiece. The mask is connected to a Nitronox 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, Nitronox 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 Nitronox 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 Nitronox cylinder.
Nitronox may be administered by personnel trained in its use (obstetric units, accident units and accident ambulances).
There is no risk of overdose with Nitronox in medical use.
Nitronox 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)
INSTRUCTIONS FOR USE
Use in accordance with the doctor's instructions.
It has been suggested that prolonged occupational exposure to high levels of nitrous oxide may affect a woman’s ability to become pregnant.
Avoid rapid opening of the valve as this could lead to re-liquefaction of the discharged gas. In its liquid form the substance in contact with the skin can cause cold burns.
Nitronox 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
STORAGE OF CYLINDERS
1. Cylinders should be stored under cover, preferably inside, kept dry and
clean and not subjected to extremes of heat or cold.
2. Cylinder should not be stored near stocks of combustible materials or
near sources of heat.
3. Warning notices prohibiting smoking or naked lights should 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. Precautions should be taken to protect cylinders from theft.
1. Cylinder valves must be opened slowly.
2. Cylinder valves should be opened momentarily prior to use to blow any grit or foreign matter out of the outlet.
Ensure that the connecting face of the pin index yoke, or regulator is clean and the sealing washer or ‘O’ ring where fitted is in good condition.
3. Where an integral valve is not used only the appropriate regulator should be used for the particular gas concerned.
4. Pipelines for medical gases should be controlled in accordance with the conditions set out in HTM 02.
5. 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 would usually be evident by a hissing noise.
2. Leaks can be found by brushing the suspected area with an approved leak detection solution
3. Sealing or joining compounds must never be used to cure a leak.
4. 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. Medical gases must only be used for medicinal purposes.
5. Smoking and naked lights must not be allowed within the vicinity of cylinders or pipeline outlets.
6. After use, cylinder valves should be closed using moderate force only and the pressure in the regulator or tailpipe released.
7. When empty, the cylinder valve must be closed.
8. Immediately return empty cylinders to the empty cylinder store for return to Medical Gas Solutions Ltd.
4.3 Contraindications
Nitronox should not be used in any condition where air is entrapped within the body and where its expansion might be dangerous, such as with:
• 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 Nitronox 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.
Nitronox 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 B12 levels 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.
Nitronox 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 Nitronox.
Care is needed in the handling and use of Nitronox gas cylinders
4.5 Interaction with other medicinal products and other forms of interaction
The nitrous oxide constituent of Nitronox inactivates vitamin B12.
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.
Therefore, there is no absolute contra-indication to its use in the first 16 weeks of pregnancy.
There are no known adverse effects in relation to breast feeding.
It has been suggested that prolonged occupational exposure to high levels of nitrous oxide may affect a woman’s ability to become pregnant.
4.7 Effects on ability to drive and use machines
The nitrous oxide constituent of Nitronox is rapidly eliminated but it is recommended that the driving, use of machinery and other psychomotor activities should, as a safety precaution, not be undertaken until 12 hours have elapsed after Nitronox analgesia.
4.8 Undesirable effects
Events such as euphoria, disorientation, sedation, nausea, vomiting,dizziness and general 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.
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 Nitronox 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
OXYGEN
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 Nitronox, 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/m3 (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
Nitronox is chemically inactive and will not react with other compounds at normal temperatures.
6.3. Shelf life
36 months.
6.4.
Special precautions for storage
Nitronox 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
Nitronox Inhalation Gas is a compressed gas mixture that is held within a pressure vessel made of a limited list of materials. These can include steel, aluminium, aluminium liners with carbon wrap on either sides of the cylinder or all over. The cylinders conform to the requirements set out in the current Carriage of Dangerous Goods and Transportable Pressure Equipment Regulations. All cylinders used for Nitronox Inhalation Gas are designed and tested to conform to these regulations.
Nitronox Inhalation Gas cylinders are fitted with a valve; the valve can be pin-index conforming to BS EN ISO 407 or an integral pressure regulator valve that is CE marked for Medical Device Regulations.
The cylinders have a variety of nominal water capacities ranging from 1 to 50 litres and are filled to 137 or 200 bar.
This gives the following range of nominal Nitronox content in litres of the cylinders at 15 C and 1013.2mbar:
428, 536, 1071, 2020, 2140, 4280, 5056, 6420, 10100.
The colour scheme for Nitronox cylinders is changing from a blue body with a blue and white quartered shoulder (top) to a white body with a blue and white quartered shoulder (top).
Your cylinder may be of either colour scheme.
6.6 Special precautions for disposal
Contact Medical Gas Solutions to refill the cylinder. Any cylinders that are no longer required should be returned to Medical Gas Solutions
7. MARKETING AUTHORISATION HOLDER
Medical Gas Solutions Ltd
Unit 19, Manor Park Industrial Estate,
Bagillt, Flint CH6 5UY
MARKETING AUTHORISATION NUMBER
8.
PL 17872/0001
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
15th September 2005/ 1st July 2011
10 DATE OF REVISION OF THE TEXT
31/07/2012