Consumer medicine information

Medical Equanox

Nitrous oxide; Oxygen

BRAND INFORMATION

Brand name

Equanox

Active ingredient

Nitrous oxide; Oxygen

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Medical Equanox.

What is in this leaflet

Please read this leaflet carefully before you receive this treatment. It provides a summary of the information known about your treatment. If you have any questions or are unsure about anything, ask your doctor.

All medicines have risks and benefits. Your doctor or healthcare professional has weighed the risks of you using Medical Equanox against the benefits they expect it will have for you.

If you have any concerns about using Medical Equanox , ask your doctor.

Keep this leaflet with you, you may want to read it again.

What Medical Equanox is used for

Medical Equanox is a gas mixture of 50% Medical Nitrous Oxide and 50% Medical Oxygen (nominal) used for pain relief.

Medical Equanox works by relieving pain for certain procedures.

Your doctor may prescribe Medical Equanox for another purpose. Ask your doctor if you have any questions about why Medical Equanox has been prescribed for you.

This medicine is available only with a doctor's prescription.

Before you use Medical Equanox

Do not take Medical Equanox if

  1. You have a condition where air is entrapped within your body and it might expand when given nitrous oxide (e.g. bowel obstruction, blocked middle ear, following a recent dive). Ask your doctor for full details of these conditions.
  2. You have been using Medical Equanox for a prolonged period without proper monitoring of your blood.
  3. You are intoxicated or heavily sedated.

You must tell your doctor if

  1. You have had a reaction to Medical Equanox or any other general anaesthetic or pain relief medication in the past.
  2. You have had a general anaesthetic.
  3. You have or have had any other health problems or medical conditions, including:
  • Low vitamin B12 levels.
  • Head injuries with impairment of consciousness.
  • Artificial, traumatic or spontaneous pneumothorax.
  • Air embolism.
  • Decompression sickness.
  • Following a recent dive.
  • Following air encephalography.
  • Sever bullous emphysema.
  • During myringoplasty.
  • Gross abdominal distension.
  • Intoxication.
  • Maxillofacial injuries.
  1. You are pregnant or intend to become pregnant. Pregnant females may experience spontaneous abortion and low birth weight babies.
  2. You have had long term usage or been chronically exposed to nitrous oxide.

Taking other medicines

Tell your doctor if you are taking any other medicines, including medicines you buy without a prescription from a pharmacy, supermarket or health food shop.

Your doctor may have more information on medicines to avoid while using Medical Equanox.

If you have not told your doctor about any of the above, tell them before you start using Medical Equanox .

How to use Medical Equanox

Medical Equanox should only be used under the supervision of your doctor or healthcare professional.

How much to use and how to use it

The amount of Medical Equanox given to you will be decided by your doctor, depending on the amount of pain relief required. It is usually given to you by breathing it through a mask or mouthpiece.

If you are elderly or have lung problems, you may need a lesser amount of Medical Equanox.

Follow all directions given to you by your doctor carefully. These directions may differ from the information contained in this leaflet.

If you do not understand the instructions, ask your doctor for help.

How long to use it

Your doctor will decide for how long you need to use Medical Equanox.

If you use too much (overdose)

As Medical Equanox is most likely to be given to you under the direction of your doctor, anaesthetist, ambulance officer, dentist or nurse, it is very unlikely you will receive an overdose. However, if this happened, quick action can be taken to maintain your breathing and replace the Medical Equanox with oxygen.

If you have any questions, then ask your doctor.

While you are taking Medical Equanox

Things you must do

Tell your doctors, dentists and pharmacists who are treating you that you are taking Medical Equanox.

Tell your doctor if you become pregnant while taking Medical Equanox.

Tell your doctor if you have taken a general anaesthetic.

Be sure to keep all of your appointments with your doctor so that your progress can be checked.

Things you must not do

Do not stop taking Medical Equanox without first checking with your doctor.

Do not drive a vehicle or operate machinery.

Side effects

Tell your doctor as soon as possible if you do not feel well while you are using Medical Equanox.

Medical Equanox may have unwanted side effects in some people. Sometimes they are serious, most of the time they are not. You may need medical treatment if you experience some of the side effects.

Ask your doctor any questions you may have.

Tell your doctor if you notice any of the following and they worry you:

  • Nausea, vomiting.
  • Headache, dizziness.

These side effects are usually mild.

Tell your doctor immediately if you notice any of the following:

  • Confusion, excitation, depression.
  • Breathing problems.
  • Heart problems.
  • Pins and needles, changes in sensation.
  • Bleeding, fits.
  • Abdominal pain, bloating.
  • Addiction.
  • Paraestsiqe in the legs.
  • Hyperflexia and weakness of the intrinsic hand muscles.

These are serious side effects. You may need urgent medical attention. Serious side effects are rare. Other side effects may occur as a result of other medications received, so check with your doctor if you have any concerns.

If any of the above happen, tell your doctor immediately or go to casualty at your nearest hospital.

Other side effects not listed above may also occur in some patients. Tell your doctor if you notice anything else that is making you feel unwell.

Ask your doctor if you don’t understand anything in this list.

Do not be alarmed by this list of possible side effects.You may not experience any of them.

After using Medical Equanox

Storage

Medical Equanox is supplied to the hospital or clinic or doctor and they will be responsible for ensuring the container is stored in accordance with the manufacturer’s instructions.

Disposal

Medical Equanox is supplied to the hospital or clinic or doctor and they will be responsible for ensuring the container is returned to the manufacturer.

Product Description

What it looks like

Medical Equanox is a clear, colourless, slightly sweet smelling, non-irritating gas. supplied in a pressurised gas cylinder with a valve. The gas cylinder contains only Medical Equanox. The gas cylinders’ colour code is a white body with a ultramarine & white triangle shoulder (plus 2 x “N”) as determined by AS4484.

Cylinder sizes include 2.8l, 9.5l, 23l, 50l, as measured by nominal water capacity.

Ingredients

Active
Nitrous oxide: 50% v/v /
Oxygen: 50% v/v.

Manufacturer/Distributor/ Supplier:

Coregas Pty Ltd.
66 Loftus Road.
Yennora. NSW.2161.
Australia

AUST R 27141.

This leaflet was prepared in June 2013.

Published by MIMS November 2019

BRAND INFORMATION

Brand name

Equanox

Active ingredient

Nitrous oxide; Oxygen

Schedule

S4

 

1 Name of Medicine

Nitrous oxide 50% v/v and oxygen 50% v/v.

2 Qualitative and Quantitative Composition

Nitrous oxide 50% v/v and oxygen 50% v/v.

3 Pharmaceutical Form

Compressed medical gas (for medicinal use only).

4 Clinical Particulars

4.1 Therapeutic Indications

Equanox is used as relief from severe pain, usually in emergency situations:
Short-term procedures which inevitably involve pain, such as wound and burn dressing, wound debridement and suturing;
Traumatic injuries;
Invasive procedures (e.g. catheterisation, sigmoidoscopy);
Changing position of limbs, manipulation or splinting;
Altering the position of a patient in pain;
Applying traction and insertion and removal of skeletal pins for traction;
Removal of radioactive intracavity gynaecological applicators;
Physiotherapy;
Renal colic;
Labour pains;
Sternum bone marrow biopsy;
Constipation;
Paediatrics;
In dental work to provide short-term analgesia for tooth extraction and other brief procedures.

4.2 Dose and Method of Administration

Routes of administration.

Equanox is administered through a face mask or tracheal tube by means of an anaesthetic apparatus. The gas is breathed in by the patient and absorbed through the lungs.
Equanox should only be administered by medical personnel trained in the appropriate techniques and in an adequate environment with access to adequate resuscitation equipment.
Cylinders should only be used in conjunction with Equanox pressure regulators.
In dentistry, the use of a double mask by the dentist and dental assistant is recommended, alternatively, a mask with adequate scavenging/ventilation should be used.

4.3 Contraindications

Hypersensitivity to nitrous oxide or any other component in the gas.
All these effects are well documented, extremely rare and may follow prolonged exposure to levels of nitrous oxide over 5,000 ppm or to frequent (more than once every two days) exposure to analgesic concentrations. Vitamin B12 inactivations have been reviewed by Nunn.
Equanox should not be used with any condition where air is entrapped within a body and where its expansion might be dangerous, such as:
the presence of intracranial air; head injuries with impairment of consciousness; artificial, traumatic or spontaneous pneumothorax; pneumopericardium; air (or gas) embolism; severe head trauma; decompression sickness; following a recent dive; following cardiopulmonary bypass or air encephalography and after intraocular gas injection in ophthalmic surgery, for example with sulphur hexafluoride (SF6) or perfluoropropane (C3F8), until the intraocular gas had been completely absorbed (due to the risk of further expansion of the gas bubble possibly leading to blindness); severe bullous emphysema; during myringoplasty; occluded middle ear; cysts; gross abdominal distension; intoxication or heavy sedation; maxillofacial injuries.
Equanox medical gas is also contraindicated:
In patients with cardiac failure or severely impaired cardiac function (e.g. after cardiac surgery), since the mild myocardio-depressive effect may cause further deterioration in heart function.
In patients presenting persistent signs of confusion, changed cognitive function or other signs that could be related to increased intra-cranial pressure as nitrous oxide may further increase the intra-cranial pressure.
In patients presenting decreased consciousness and/or co-operability because of the risk for loss of protecting reflexes.
In patients presenting with a vitamin B12 or folic acid deficiency or genetic perturbation in this system.
In patients with facial injury where use of a face mask may present difficulties or risks.
Equanox should not be used as an analgesic agent for more than 24 hours without monitoring of peripheral blood for features of megaloblastic anaemia and leukopenia.
There are no absolute contraindications to the use of oxygen, but the inspired concentration should be limited in the case of premature infants and patients with chronic bronchitis and emphysema or whose respiration is dependent upon hypoxic drive.

4.4 Special Warnings and Precautions for Use

General.

Equanox should only be administered by medical personnel with access to adequate resuscitation equipment (see Section 4.2 Dose and Method of Administration).
Addiction to and abuse of nitrous oxide has been reported. Delirium has been reported upon withdrawal.

Occupational exposure to nitrous oxide.

Nitrous oxide is a simple asphyxiant in the absence of oxygen. Classified as hazardous according to criteria of Worksafe Australia.
Reduced fertility in medical and paramedical personnel has been reported after repeated exposure to nitrous oxide in inadequately ventilated rooms. It is not currently possible to confirm or exclude the existence of any causal connection between these cases and nitrous oxide exposure. See Section 4.6 Fertility, Pregnancy and Lactation, Effects on fertility.
It is important that the nitrous oxide content in the ambient air is kept as low as possible and well below the nationally set limit value.
Scavenging of waste nitrous oxide gas should be used to reduce operating theatre and equivalent treatment room levels to a level below 25 ppm of nitrous oxide (worksafe exposure standard TLV TWA).
Rescue personnel are advised to monitor nitrous oxide concentration before entering confined spaces and poorly ventilated areas which have been contaminated by a 50% medical oxygen/50% medical nitrous oxide leak. Chronic occupational exposure to nitrous oxide may lead to bone marrow or neurological impairment (see Section 4.6 Fertility, Pregnancy and Lactation, Use in pregnancy; and below: Interference with vitamin B12 metabolism leading to neurological and bone marrow toxicity).

Chronic exposure.

Care should be taken with long term usage of nitrous oxide. Chronic exposure to nitrous oxide, including abuse, can inactivate vitamin B12 and may result in polyneuropathy, megaloblastic anaemia, bone marrow depression and reproductive effects (see Section 4.8 Adverse Effects (Undesirable Effects)). A full blood examination should be performed in abusers, professionals chronically exposed and patients receiving ongoing therapy for evidence of megaloblastic change in red blood cells and hypersegmentation of neutrophils.

Interference with vitamin B12 metabolism leading to neurological and bone marrow toxicity.

The nitrous oxide component of Equanox causes inactivation of vitamin B12 (a co-factor of methionine synthesis), which interferes with folic acid metabolism. Nitrous oxide inhibits methionine synthetase which contributes to the conversion of homocysteine to methionine. The inhibition of this enzyme affects/reduces the formation of thymidine, which is an important part of DNA formation. Thus, DNA synthesis is impaired following prolonged nitrous oxide administration. These disturbances can result in megaloblastic bone marrow changes and possibly polyneuropathy and/or subacute combined degeneration of the spinal cord (see Section 4.8 Adverse Effects (Undesirable Effects)). The effect on DNA synthesis is one of the probable reasons for the influence of nitrous oxide on blood formation and the foetal damage seen in animal studies.
After inhaling nitrous oxide, leucopenia and megaloblastic anaemia have been described, in some cases fatal. A polyneuritic type of neuropathy and spinal cord sclerosis can appear during chronic administration of high concentrations of nitrous oxide.
Administration of Equanox for long periods should be applied with caution because of the potential risk for clinical manifestations from the inhibitory effects on the methionine synthase. Where there is prolonged continuous use or recurrent use, monitoring of peripheral blood for features of megaloblastic anaemia and leucopenia is recommended.
Neurological toxicity can occur without anaemia or macrocytosis and with B12 levels in the normal range.
Equanox should be used with caution in patients at risk of vitamin B12 or folic acid deficiency, i.e. those with deficient intake or absorption of vitamin B12/folic acid or genetic perturbations in this system, and in immunocompromised patients.
In patients with undiagnosed subclinical deficiency of vitamin B12, neurological toxicity has occurred after single exposures to nitrous oxide during general anaesthesia.
Other analgesic therapies should be considered in patients showing signs of vitamin B12/folate deficiency. See Section 4.3 Contraindications.

Other precautions.

Nitrous oxide alone may increase pulse rate and have depressant effects on respiration.
Nitrous oxide should be used with caution in patients with severe hypotension.
Equanox can, by diffusion of nitrous oxide, induce increase in middle ear pressure. Prolonged exposure may result in middle ear damage and rupture of ear drums.
In patients taking other centrally acting depressant medicinal products, e.g. morphine derivatives and/or benzodiazepines, concomitant administration of Equanox may result in increased sedation, and consequently have effects on respiration, circulation and protective reflexes. (See Section 4.5 Interactions with Other Medicines and Other Forms of Interactions.)
Equanox should be used with caution in patients with compromised chemoreceptor sensitivity/function (e.g. chronic obstructive pulmonary disease - COPD) due to the relative high content (50 vol.%) of oxygen. Inhalation of high doses of oxygen may in such patients cause respiratory depression and increase in PaCO2.
After cessation of Equanox administration, nitrous oxide rapidly diffuses from blood to the alveoli. Due to the rapid wash-out dilution, a decrease of the alveolar oxygen concentration, diffusion hypoxia might occur.
At high altitude or in the presence of disorders affecting oxygenation, the amount of nitrous oxide required will vary. Users should be aware that Equanox contains a fixed combination of 50% Nitrous oxide/50% oxygen.
Smoking is prohibited when the product is in use and no naked flames should be allowed.
Nitrous oxide passes into gas containing spaces in the body faster than Nitrogen passes out. Prolonged usage may result in bowel distension and expansion of other non-vented gas containing cavities.

Use with caution in the following circumstances.

Administration of 50% medical oxygen/50% medical nitrous oxide more frequently than every four days should be accompanied by routine blood cell counts for evidence of megaloblastic change in red blood cells and hypersegmentation of neutrophils.

Use of gas cylinders.

Cylinders should be kept out of the reach of children.
Care is needed in the handling and use of gas cylinders containing Equanox.
Equanox is stored in high pressure gas cylinders under pressure at ambient temperature. Cylinders should be used in the vertical position with the valve uppermost.
Equanox cylinders must be stored above 0°C. At temperatures below this the nitrous oxide component may separate, leading to risk for potential inhalation of a hypoxic gas mixture. Should this occur the cylinder should be placed in a warm room for at least 2 hours, then rolled horizontally to and fro for at least 5 mins to remix the components.
Cylinder should not have been stored below 0°C. Overdose can arise as the result of inappropriate storage of the gas cylinders at temperatures below 0°C.
For further information, see Section 6.4 Special Precautions for Storage.
The normal precautions required in the storage and use of medical gas cylinders are applicable. Cylinders should be stored away from sources of ignition, poisons, flammable or combustible materials. They should be secured upright, in a secure area, below 45°C, on a dry well ventilated area constructed of non-combustible material with a firm, level floor (preferably concrete) away from heavy traffic and emergency exits.
Additional information is contained in the Material Safety Data Sheet for Equanox.
Worksafe exposure standard TLV TWA for nitrous oxide is 25 ppm.

Check the following before use.

Cylinder should not have been stored below 0°C. See above, Use of gas cylinders.
Nitrous oxide (in Equanox) is non-flammable but strongly supports combustion (including some materials which do not normally burn in air). It is highly dangerous when in contact with oils, greases, tarry substances and many plastics due to the risk of spontaneous combustion with high pressure gases.
Check that the dispensing equipment connection matches cylinder valve outlet.
Check that the cylinder pressure is a true indicator of quantity remaining in cylinder.

Preparation for use.

Cylinder valves should be opened momentarily prior to use to blow any foreign matter out of the outlet.
Ensure that the connecting face on the yoke, manifold or regulator is clean and the sealing washer or 'O' ring where fitted is in good condition.
Cylinder valves must be opened slowly.
Only the appropriate regulator should be used for the particular gas concerned.
Cylinder valves and any associated equipment must never be lubricated and must be kept free from oil and grease.

Leaks.

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.
There are no user serviceable parts associated with these valves, do not attempt to correct any problems with leakage from any part of the valve itself. Label any faulty containers appropriately and return them to Coregas for repair.
Sealing or jointing compounds must never be used to cure a leak.
Never use excessive force when connecting equipment to cylinders.

Handling of cylinders.

Cylinders should be handled with care and not knocked violently or allowed to fall.
Cylinders should only be moved with the appropriate size and type of trolley.
When in use cylinders should be firmly secured to a suitable cylinder support.
Cylinders containing liquefiable gas must always be used vertically with the valve uppermost.
Medical gases must only be used for medicinal purposes.
Smoking and naked lights must not be allowed within the vicinity of cylinders or pipeline outlets.
After use cylinder valves should be closed using moderate force only and the pressure in the regulator or tailpipe released.
When empty the cylinder valve must be closed.
Immediately return used cylinders to the used cylinder store for return to Coregas.

Use in the elderly.

No data available.

Paediatric use.

Paediatric neurotoxicity.

Some published studies in children have observed cognitive deficits after repeated or prolonged exposures to anaesthetic agents early in life. These studies have substantial limitations, and it is not clear if the observed effects are due to the anaesthetic/analgesic/sedation drug administration or other factors such as the surgery or underlying illness.
Published animal studies of some anaesthetic/analgesic/sedation drugs have reported adverse effects on brain development in early life and late pregnancy. The clinical significance of these nonclinical findings is yet to be determined.
With inhalation or infusion of such drugs, exposure is longer than the period of inhalation or infusion. Depending on the drug and patient characteristics, as well as dosage, the elimination phase may be prolonged relative to the period of administration.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

There are no major incompatibilities with 50% medical oxygen/50% medical nitrous oxide.
Medical nitrous oxide inactivates vitamin B12.
Nitrous oxide and CNS depressants may lead to increased CNS depression, increased respiratory depression and increased hypotensive effects.
Nitrous oxide and opioids together may lead to further circulatory depression. High dose fentanyl with nitrous oxide may decrease heart rate and cardiac output.
The pulmonary toxicity associated with paraquat and drugs such as bleomycin, amiodarone, nitrofurantoin and antibiotics similar to nitrofurantoin may be exacerbated by inhalation of increased concentration of oxygen.
The pharmacokinetic activity of oxygen is modified by changes in the blood carbon dioxide tension but this has little significance.

Methotrexate.

Nitrous oxide potentiates the effect of methotrexate on folate metabolism, yielding increased toxicity such as severe, unpredictable myelosuppression, stomatitis and neurotoxicity with intrathecal administration. Avoid concomitant use of nitrous oxide in patients receiving methotrexate.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

See Section 4.4 Special Warnings and Precautions for Use, Occupational exposure to nitrous oxide.
The fecundity of female dental assistants was reduced for those women working with unscavenged nitrous oxide. Similarly, fecundity was reduced in Swedish female midwives exposed to nitrous oxide while assisting with deliveries.
(Category A)
Pregnant females may experience spontaneous abortion and low birth weight babies.
The nitrous oxide component of Equanox interferes with vitamin B12/folic acid metabolism (see Section 4.4 Special Warnings and Precautions for Use, Interference with vitamin B12 metabolism leading to neurological and bone marrow toxicity). Inhibition of the methionine synthase may cause adverse effects during early stages of pregnancy.
Animal studies have demonstrated that high concentration or prolonged exposure during particular stages of pregnancy can induce teratogenic effects. The potential risk for humans is unknown.
Epidemiological studies suggest an increased risk of spontaneous abortion and low birth weight in off-spring in female workers employed in operating theatres and dental surgeries. These findings are controversial.
Published animal studies of some anaesthetic/analgesic/sedation drugs have reported adverse effects on brain development in early life and late pregnancy.
Published studies in pregnant and juvenile animals demonstrate that the use of anaesthetic/analgesic/sedation drugs that block NMDA receptors and/or potentiate GABA activity during the period of rapid brain growth or synaptogenesis may result in neuronal and oligodendrocyte cell loss in the developing brain and alterations in synaptic morphology and neurogenesis when used for longer than 3 hours. These studies included anaesthetic agents from a variety of drug classes.
Mild skeletal teratogenic changes have been observed on 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 50% medical oxygen/50% medical nitrous oxide is toxic to the human foetus.
Inhalation anaesthetics cross the placenta.
Studies of operating room personnel chronically exposed to low concentrations of inhalation anaesthetics show that pregnancies in female personnel and the wives of male personnel may be subject to increased incidences of spontaneous abortions, stillbirths and possibly birth defects. However, the methods used in obtaining and interpreting the data in these studies have been questioned. Studies on dental staff's exposure to anaesthetic gases had conflicting results. One study showed an increased risk of spontaneous abortion among dental assistants exposed to nitrous oxide.
 It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, Equanox should not be administered to a nursing woman.

4.7 Effects on Ability to Drive and Use Machines

50% medical oxygen/50% medical nitrous oxide is rapidly eliminated but it is recommended that driving, use of machinery and other psycho-motor activities should not be undertaken until 12 hours have elapsed after nitrous oxide anaesthesia.
The influence on cognitive capabilities by the nitrous oxide component of Equanox can persist for several hours after administration has stopped.
When used as the sole analgesic/sedative agent, driving and use of complex machinery is not recommended following cessation of Equanox until the patient has returned to their initial mental status as judged by the attending healthcare professional.
Additional care is needed when Equanox is administered to a patient who has been given concomitant medication.

4.8 Adverse Effects (Undesirable Effects)

The undesirable effects listed in Table 1 are derived from public domain scientific medical literature and post marketing safety surveillance.

Haematological.

The use of 50% medical oxygen/50% medical nitrous oxide 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. These disturbances result in symptoms similar to vitamin B12 deficiency and megaloblastic bone marrow changes. Bone marrow depression with resultant leukopenia, thrombocytopenia and severe megaloblastic anaemia have been noted. Exceptionally heavy occupational exposure and addiction have resulted in myeloneuropathy and subacute combined degeneration.
These effects include rarely - drowsiness, confusion, paraesthesiae in the legs, hyper-reflexia and weakness of the intrinsic hand muscles.
If these effects occur, usage of Equanox should be stopped and daily vitamin B12 replacement administered. Effects should then be expected to be reversed gradually.
All these effects are well documented, extremely rare and may follow prolonged exposure to levels of nitrous oxide over 5,000 ppm or to frequent (more than once every two days) exposure to analgesic concentrations.

Cardiovascular.

Cardiovascular depression, hypotension, arrhythmia, increased pulmonary vascular resistance.

Respiratory.

Hypoxia, diffusion hypoxia, asphyxia, pulmonary toxicity.

Neurological.

Confusion, CNS excitation and depression, raised intracranial pressure, anxiolytic effects, euphoria, neuropathy, seizures/convulsions, drowsiness. Exceptionally heavy occupational exposure or frequent use and addiction have resulted in myeloneuropathy (including polyneuropathy) and subacute combined degeneration of the cord.

Gastrointestinal.

Bowel distension following prolonged usage.

Pregnancy and lactation.

See Section 4.6 Fertility, Pregnancy and Lactation.
Prolonged occupational exposure to high levels of nitrous oxide may affect a woman's ability to become pregnant.

Other effects.

Nitrous oxide passes into all gas containing spaces in the body faster than nitrogen passes out.
The main contra-indications which follow from this are listed above, but in addition prolonged anaesthesia may result in bowel distension, middle ear damage and rupture of ear drums.
Addiction to and abuse of nitrous oxide has been reported.

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

Symptoms and signs.

Inappropriate, unwitting or deliberate inhalation of nitrous oxide will ultimately result in unconsciousness, passing through stages of increasing lightheadedness and intoxication, and, if the victim were to be within a confined space, death from anoxia could result. Other signs may include: bradycardia, respiratory depression, cardiovascular depression and severe hypotension.

Treatment.

The treatment is fresh air, mouth-to-mouth resuscitation and, if necessary, the use of an oxygen resuscitator.
For information on the management of overdose, contact the Poisons Information Centre on 131126 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Nitrous oxide is an analgesic and a weak anaesthetic. Pain reduction is achieved at a concentration of around 25%. 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.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption.

Nitrous oxide is not very soluble in water but is fifteen times more soluble than oxygen. Water dissolves nitrous oxide, taking 100 volume % and blood plasma 45 volume %.

Distribution.

Nitrous oxide at a concentration of 50% (Equanox) is a potent analgesic and only slightly soluble. The advantage of this is that when concentrations of not greater than 50% are used, induction of analgesia and recovery occur quickly.
The blood/gas partition coefficient of nitrous oxide at 37°C is 0.46 compared with that of nitrogen of 0.015, causing nitrous oxide to expand into internal gas spaces.
Nitrous oxide passes into gas containing spaces in the body faster than nitrogen passes out.

Metabolism.

Not applicable.

Excretion.

Nitrous oxide is eliminated unchanged from the body mostly by the lungs.

5.3 Preclinical Safety Data

Genotoxicity.

An increased frequency of chromosomal aberrations was observed in bone marrow cells and spermatogonia of rats treated with a mixture of nitrous oxide and halothane. Nitrous oxide also caused an increased incidence of sister chromatid exchanges (SCE) in human lymphocytes in vitro.
Clinical studies have suggested that nitrous oxide may be associated with genotoxic events. DNA strand breaks were reported in surgical patients treated with isoflurane-nitrous oxide-oxygen post-surgery. An increased frequency of SCE, but not micronuclei, was found in the lymphocytes of operating room personnel exposed to nitrous oxide and isoflurane. An increase in SCE was also found in operating room personnel exposed to halothane and nitrous oxide.

Carcinogenicity.

No data available.

6 Pharmaceutical Particulars

6.1 List of Excipients

No excipients present.

6.2 Incompatibilities

There are no major incompatibilities with nitrous oxide.

6.3 Shelf Life

Not applicable.

6.4 Special Precautions for Storage

Equanox cylinders must be stored above 0°C.
The normal precautions required in the storage of medical gas cylinders as described below are applicable.
Please refer to Commonwealth, State and Territory Dangerous Goods legislation and the appropriate Australian Standards e.g. AS 4332.
Cylinders should be stored under cover, preferably inside, kept dry and clean and not subjected to extremes of heat or cold.
Cylinders should not be stored near stocks of combustible materials or near sources of heat.
Warning notices prohibiting smoking and naked lights must be posted clearly.
Emergency services should be advised of the location of the cylinder store.
Medical cylinders containing different gases should be segregated and identified within the store.
Full and empty cylinders should be stored separately. Full cylinders should be used in strict rotation.
Cylinders must not be repainted, have any markings obscured or labels removed.
D size cylinders and larger should be stored vertically; C size cylinders can be stored horizontally.
Precautions should be taken to protect cylinders from theft.
Cylinders should be kept out of the reach of children.

6.5 Nature and Contents of Container

Equanox is supplied in aluminium or steel gas cylinders with a PIN index valve, suitable for the filling pressure applied for the product.
The types of cylinders normally used are specified in Table 2.

6.6 Special Precautions for Disposal

The cylinder pack should not be disposed of but must be returned to the supplier.

6.7 Physicochemical Properties

Oxygen.

Chemical structure.


CAS number.

7782-44-7.
MW: 32.0.

Nitrous oxide.

Chemical structure.


CAS number.

10024-97-2.
MW: 44.01.
Equanox is a homogenous gas mixture of medical nitrous oxide 50% v/v and medical oxygen 50% v/v.

Nitrous oxide.

Complies with European Pharmacopoeia specification 1997 (see Table 3).

Physical data - nitrous oxide.

Molecular weight 44.01.
Physical state in cylinder: Gas at ambient temperature.
Specific gravity of gas at 15°C and 101.3 kPa: 1.53.
Density of gas at 15°C and 101.3 kPa: 1.875 kg/m3.
Combustion characteristics: Non flammable. Strongly supports combustion.
Sweet smelling colourless gas
Boiling point: -88.6°C (at 1 bar).
Nitrous oxide is not very soluble in water but is fifteen times more soluble than oxygen. Water dissolves nitrous oxide, taking 100 volume % and blood plasma 45 volume %.

Chemical characteristics.

Nitrous oxide is an oxidising substance which will support combustion of materials which may not normally burn in air. The molecule is stable and comparatively unreactive at ordinary temperatures. At elevated temperatures it decomposes to nitrogen and oxygen. Nitrous oxide will react with powerful reducing agents such as phosphine, stannous chloride and hydrogen. Rust may cause ignitions.

Medical oxygen.

Specification - medical oxygen.

Complies with European Pharmacopoeia specification 1997.
Purity 99.5% (min).
Carbon dioxide 300.0 vpm (max).
Carbon monoxide 5.0 vpm (max).

Physical data - medical oxygen.

Molecular weight 32.00.
Physical state in cylinder: Gas.
Specific gravity of gas at 15°C and 101.3 kPa: 1.106.
Density of gas at 15°C and 101.3 kPa: 1.355 kg/m3.
Combustion characteristics: Non flammable. Strongly supports combustion.

7 Medicine Schedule (Poisons Standard)

S4 - Prescription only medicine.

Summary Table of Changes