Consumer medicine information

Air Liquide Healthcare Nitronox 50% Nitrous Oxide and 50% Oxygen Mixture Gas Medicinal

Nitrous oxide; Oxygen

BRAND INFORMATION

Brand name

Air Liquide Australia Limited Nitronox

Active ingredient

Nitrous oxide; Oxygen

Schedule

What is in this leaflet

This leaflet answers some common questions about Nitronox. It does not contain all the available information.

It does not take the place of talking to your doctor, anaesthetist, surgeon or dentist.

All medicines have risks and benefits. Your doctor or dentist has weighed the risks of you using Nitronox against the benefits they expect it will have for you.

If you have any concerns about using Nitronox, ask your doctor or dentist.

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

What Nitronox is used for

Nitronox is a gas mixture of 50% Medical Nitrous Oxide and 50% Medical Oxygen used for general anaesthesia.

Nitronox works by relieving pain for certain procedures.

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

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

Before you use Nitronox

When you must not use it

Do not use Nitronox if:

You have an allergy to nitrous oxide or any other component in the gas or have had an allergic reaction in the past.
You have a condition where air is entrapped within your body and it might expand when given Nitronox (eg bowel obstruction, blocked middle ear, following a recent dive). Ask your doctor for full details of these conditions.
You have been using it for a prolonged period without proper monitoring of your blood.
You are intoxicated or heavily sedated
You have recently had any surgery on our eyes or ears where injections of gas have been used.

Do not use Nitronox if the cylinder is damaged or shows signs of tampering or it has degraded.

Before you start to use it

You must tell your doctor or dentist if:

You are allergic to any other medicines, foods, dyes or preservatives.
You have had a reaction to nitrous oxide or any other general anaesthetic or pain relief medication in the past.
You have had a general anaesthetic or surgery in the past.
You have or have had any other health problems or medical conditions, including:

A condition known as malignant hyperthermia or a family history of it.
Low blood pressure
Low vitamin B12 levels
Problems with addiction to medicines
Bone marrow problems including various cells in the blood
Neurological diseases
Conditions in which air is entrapped within the body

You are pregnant or intend to become pregnant.

Your doctor or dentist will discuss the risks and benefits of using Nitronox when pregnant.

You are breastfeeding or wish to breastfeed.

Your doctor or dentist will discuss the risks and benefits of using Nitronox when breastfeeding.

Care should be taken when using Nitronox as it is stored under high pressure in gas cylinders. Contact with eyes or skin may result in cold burns.

There are also safe working exposure levels and important storage instructions. Please discuss these with your doctor if you have any questions.

You have had long term usage or been chronically exposed to Nitronox.

Taking other medicines

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

Some commonly used medicines that may interfere with Nitronox include:

Pain relievers
Anaesthetics
Methotrexate
Medicines which may affect your nervous system
Medicines which may interfere with Vitamin B12 and/or folate metabolism

These medicines may be affected by Nitronox or may affect how well it works. You may need to take different amounts of your medicine or you may need to take different medicines.

Some medicines may affect the way others work. Ask what to do when using Nitronox with other medicines.

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

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

How to use Nitronox

Nitronox should only be used under the supervision of your doctor or dentist.

How much to use and how to use it

The amount of Nitronox given to you will be decided by your doctor or dentist. It is usually given to you by breathing it through a mask.

Follow all directions given to you by your doctor or dentist 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 Nitronox.

If you use too much (overdose)

As Nitronox is most likely to be given to you in hospital under the direction of your doctor, it is very unlikely you will receive an overdose.

However, if this happened, quick action can be taken to maintain your breathing.

If you have any questions then ask your doctor.

After you have used Nitronox

Things you must not do

Following analgesia:
Ask your doctor or dentist when it is safe for you to drive, operate machinery or perform activities following the use of Nitronox.

Side effects

Tell your doctor or dentist as soon as possible if you do not feel well while you are using Nitronox.

Nitronox may have unwanted side effects in some people. All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical treatment if you get some of the side effects.

Ask your doctor any questions you may have.

Rare cases of respiratory depression in newborns have been observed, when using nitrous oxide close to delivery, newborns should be supervised for possible side effects.

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

Nausea, vomiting
Headache, dizziness, drowsiness

These side effects are usually mild.

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

Confusion, excitation and depression of the central nervous system
Breathing problems
Anxiety, agitation, disorientation, hallucination
Heart problems
Pins and needles, changes in sensation
Blood disorders
Seizures
Abdominal pain, bloating
Addiction
impaired vision
Ear pain
Vitamin B12 deficiency

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 your operation or other medications and anaesthetics received so check with your doctor or dentist if you have any concerns.

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

Other side effects not listed above may also occur in some patients.

Tell your doctor or dentist if you notice anything else that is making you feel unwell.

Ask your doctor or dentist 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 Nitronox

Storage

Nitronox is stored at ambient temperature in cylinders by your doctor or hospital under specific instructions.

Disposal

All cylinders are the property of the manufacturer as indicated on the label. All cylinders are returnable to the manufacturer

Product Description

What it looks like

Nitrous oxide is a sweet smelling, colourless, non-irritating gas. Oxygen is a colourless, odourless gas. Nitronox supplied in a cylinder with a white body and a ultramarine shoulder.

Single cylinders are available in Cylinder sizes C (0.5 m³), D (1.7 m³), E (4.3 m³) and G (8.8 m³).

Ingredients

Active Ingredient
Nitrous oxide- 50%
Oxygen – 50%

Sponsor

Air Liquide Healthcare Pty Ltd
Level 4, Suite 4
247 Coward Street
Mascot, NSW 2020

Australian Registration Number

AUST R 32752

This leaflet was prepared on November 2022.

Published by MIMS March 2023

BRAND INFORMATION

Brand name

Air Liquide Australia Limited Nitronox

Active ingredient

Nitrous oxide; Oxygen

Schedule

1 Name of Medicine

Nitrous oxide and oxygen.

2 Qualitative and Quantitative Composition

The specifications for each of the main components are presented separately.

Nitrous oxide.

Complies with the requirements of the current European Pharmacopoeia monograph for nitrous oxide, N₂O.
Nitrous oxide: 98.0% v/v minimum.
Carbon dioxide: 300 ppm v/v maximum.
Carbon monoxide: 5 ppm v/v maximum.
Oxides of nitrogen (NO/NO₂): 2 ppm v/v maximum.
Water (vapour): 67 ppm v/v maximum.

Oxygen.

Complies with the requirements of the current European Pharmacopoeia monograph for oxygen, oxygen, O₂.
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.
Nitronox is a homogenous gas mixture of oxygen and nitrous oxide in equal volumetric proportions.
Nitrous oxide is the active ingredient.
Nitrous oxide is a sweet smelling colourless non-irritating gas. Oxygen is a colourless, odourless and tasteless gas. Nitrous oxide is not very soluble in water and has a low solubility in blood and tissues.

3 Pharmaceutical Form

Compressed colourless medical gas mixture (for medicinal use only).

4 Clinical Particulars

4.1 Therapeutic Indications

Nitrous oxide with oxygen (Nitronox) is indicated in adults and children for analgesia.

4.2 Dose and Method of Administration

Nitronox is self-administered and inhaled via a demand valve through a facemask or mouthpiece. The gas is breathed in by the patient on demand and absorbed through the lungs.
Nitronox should only be administered by medical personnel trained in the appropriate techniques and in an adequate environment.
Cylinders should only be used in conjunction with special Nitronox gas pressure regulators and demand valves.

4.3 Contraindications

Hypersensitivity to nitrous oxide or any other component in the gas is a contraindication.
When 100% O2 ventilation is required.
Nitrous oxide 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 injury; artificial, traumatic or spontaneous pneumothorax; following air encephalography; air gas embolism; decompression sickness; following a recent dive; severe bullous emphysema; during myringoplasty; occluded middle ear; inner ear and sinus surgery cysts; gross abdominal distension; maxillofacial injuries, following cardiopulmonary bypass and if air has been injected into the epidural space to determine the placement of the needle for epidural anaesthesia.
Nitrous oxide should not be used on intoxicated or heavily sedated patients.
Patients having received recent intraocular injection of gas (such as SF6, C3F8, C2F6) as long as an intraocular gas bubble persists or within 3 months after the last injection of an intraocular gas. The expansion of an intraocular gas bubble by nitrous oxide can cause severe visual impairment (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions; Section 4.8 Adverse Effects (Undesirable Effects)).
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.
Any altered state of consciousness, preventing the patient from co-operating.

4.4 Special Warnings and Precautions for Use

Nitrous oxide causes inactivation of vitamin B₁₂ (a co-factor of methionine synthase) which interferes with folate metabolism.
Assessment of vitamin B₁₂ levels should be considered in people with risk factors for vitamin B₁₂ deficiency prior to using nitrous oxide. Haematological assessment should include assessment for megaloblastic change in red cells and hypersegmentation of neutrophils. Neurological toxicity can occur without anaemia or macrocytosis and with vitamin B₁₂ levels in the normal range. Risk factors may include alcoholic patients, patients suffering from anaemia, or atrophic gastritis, those with vegetarian diet, or recent use of medications that interfere with vitamin B₁₂ and/or folate metabolism (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions; Section 4.8 Adverse Effects (Undesirable Effects)).
There is also evidence that vitamin B₁₂ deficiency is associated with depression, organic psychosis.
In the event of obstruction of the Eustachian tube, an earache and/or middle ear disorders and/or a tympanic rupture may be observed with the increase in pressure in the tympanic cavity (see Section 4.8 Adverse Effects (Undesirable Effects)).
Intracranial pressure should be monitored closely in patients at risk of intracranial hypertension as an increase of intracranial pressure has been observed during the administration of nitrous oxide in some patients with intracranial disorders (see Section 4.8 Adverse Effects (Undesirable Effects)).

Asphyxia.

Nitrous oxide is a simple asphyxiant in the absence of oxygen. Classified as hazardous according to the criteria of Worksafe Australia.

Addiction.

Addiction and abuse of nitrous oxide have been reported. Delirium has been reported upon withdrawal. Caution should be exercised in people with a known history of substance abuse in healthcare professionals with occupational exposure to nitrous oxide.
Abuse, misuse and diversion: due to euphoric effects of nitrous oxide (see Section 4.8 Adverse Effects (Undesirable Effects)), nitrous oxide may be sought and abused for recreational use.

Prolonged use.

Care should be taken with long term usage of nitrous oxide. Chronic exposure to nitrous oxide, such as in 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.
After inhaling nitrous oxide for 5-7 days, leucopenia and megaloblastic anaemia have been described, in some case fatal. A polyneuritic type of neuropathy and spinal cord sclerosis can appear during chronic administration of high concentrations of nitrous oxide. Where there is prolonged exposure, monitoring of peripheral blood for features of megaloblastic anaemia and leucopenia is recommended.
Vitamin B₁₂ supplements should be given in the case of repeated and prolonged administration.

Scavenging.

Scavenging of waste nitrous oxide gas should be used to reduce operating theatre and equivalent treatment room levels to a level below 25 ppm exposure limit 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 that have been contaminated by a 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).
Rooms in which nitrous oxide is used must be equipped with a satisfactory scavenging or ventilation system to maintain nitrous oxide levels in the room to a minimum and below the Australian occupational exposure limit.

At altitude.

At high altitude or in the presence of disorders affecting oxygenation, the amount of nitrous oxide required will vary. Nitronox contains 50% nitrous oxide/ 50% oxygen.

Prolonged use.

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.

Other.

Nitrous oxide should be used with caution in patients with severe hypotension or those at risk of vitamin B₁₂ deficiency disorders.
Nitrous oxide has not been known to trigger malignant hyperthermia (see Section 4.8 Adverse Effects (Undesirable Effects)).
Smoking is prohibited when the product is in use and no naked flames should be allowed.
Nitrous oxide is non-flammable but strongly supports combustion (including some materials which do not normally burn in air). It is highly dangerous when nitrous oxide comes into contact with oils, grease and tarry substances due to the risk of spontaneous combustion.
See Section 6.5 Nature and Contents of Container for further information.

Use in the elderly.

No data available.

Paediatric use.

Nitrous oxide may in rare cases cause respiratory depression in the neonate (see Section 4.8 Adverse Effects (Undesirable Effects)). The neonate should be checked for possible respiratory depression when nitrous oxide is used around childbirth.

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 finding 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.

There are no known significant effects on laboratory tests, other than those associated with megaloblastic anaemia.
When administered with oxygen, self-administration should be preferred to allow the assessment of the level of consciousness.
Attentive monitoring is required in patients taking concomitantly central nervous system depressant drugs and in particular opiates and benzodiazepines, because of the increased risk of deep sedation (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

4.5 Interactions with Other Medicines and Other Forms of Interactions

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 use of nitrous oxide interacts in synergy with methotrexate on folate metabolism, yielding increased toxicity such as severe, unpredictable myelosuppression, stomatitis and neurotoxicity, following methotrexate administration including intrathecal routes.
The pharmacokinetic activity of oxygen is modified by changes in the blood carbon dioxide tension but this has little clinical significance.

Combinations which are contraindicated.

Patients having received recent intraocular injection of gas (such as SF6, C3F8, C2F6) as long as an intraocular gas bubble persists or within 3 months after the last injection of an intraocular gas. The expansion of an intraocular gas bubble by nitrous oxide can cause severe visual impairment (see Section 4.3 Contraindications; Section 4.8 Adverse Effects (Undesirable Effects)).

Combinations requiring precautions for use.

Medications that interfere with vitamin B12 and/or folate metabolism can potentiate the inactivation of vitamin B12 by nitrous oxide (see Section 4.4 Special Warnings and Precautions for Use; Section 4.8 Adverse Effects (Undesirable Effects)).
Potentialisation of hypnotic effects of central nervous system depressant drugs (opiates, benzodiazepines and other psychotropic drugs) may occur when combined with nitrous oxide (see Section 4.4 Special Warnings and Precautions for Use).

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

The germ cells of mice exposed to nitrous oxide for 14 weeks (50% nitrous oxide, 4 hours/day) showed no evidence of toxic effects due to nitrous oxide.
The fecundity of female dental assistants was reduced by 60% for those women working greater than or equal to 5 hours per week with unscavenged nitrous oxide. Similarly, fecundity was reduced in a Swedish study of midwives in those women assisting at more than 30 deliveries per month.
(Category A)
When nitrous oxide is used close to delivery, newborns should be supervised for possible adverse effects (see Section 4.4 Special Warnings and Precautions for Use; Section 4.8 Adverse Effects (Undesirable Effects)).
Inhalation anaesthetics cross the placenta. Treatment of rats with nitrous oxide (75% or 60% for each 24 hour period during organogenesis) resulted increased incidences of resorptions (days 8 and 11 of gestation), visceral abnormalities, (day 8, right sided aortic arch and left-sided umbilical artery) and minor skeletal anomalies (days 8 and 9).
Increased rates of resorptions, decreased fetal size and skeletal abnormalities have been reported in rats exposed to nitrous oxide concentrations of 0.1% throughout gestation. There were no adverse effects on the fetuses of mice exposed to 50% nitrous oxide during organogenesis.
There was no evidence of teratogenic effects in pregnant women exposed to single, brief anaesthetic exposure to nitrous oxide during pregnancy.
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. Another showed no increased risk for dental assistants either practising in private clinics or working in dental school services (OR 0.4). Others demonstrated increased risk of spontaneous abortion among dental assistants exposed to nitrous oxide for 3 or more hours weekly in places without scavenging systems. A study of Swedish midwives exposed to nitrous oxide in more than 50% of deliveries showed no increased risk of spontaneous abortion (OR 0.95). The effect of scavenging was excluded because many midwives were unsure about whether such equipment had been present in the delivery rooms. Several animal studies (in which operating room conditions were simulated) have failed to show fetotoxic or teratogenic effects following chronic exposure to male and/or female animals to low concentrations of inhalation anesthetics prior to and/or during gestation.
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 and 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.
It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when nitrous oxide is administered to a nursing woman.

4.7 Effects on Ability to Drive and Use Machines

Nitrous oxide is rapidly eliminated from the lungs and little data exists on the effects of Nitronox on the ability to drive and use machinery.
After stopping administration of nitrous oxide and in particular after prolonged administration, outpatients who must drive or use machines should be monitored until they have recovered the same state of alertness as before administration.

4.8 Adverse Effects (Undesirable Effects)

General.

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.
Addiction.

Cardiovascular.

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

Respiratory.

Hypoxia, diffusion hypoxia, asphyxia, pulmonary toxicity, respiratory depression (in the neonate, when nitrous oxide was used during delivery around childbirth - see Section 4.4 Special Warnings and Precautions for Use).

Neurological.

Headache, disorientation, dizziness, confusion, CNS excitation and depression, raised intracranial pressure, anxiolytic effects, euphoria, neuropathy, paresthesia, excessive sedation, generalized seizures, seizures, drowsiness. Exceptionally heavy occupational exposure and addiction have resulted in myeloneuropathy and subacute combined degeneration of the cord.

Psychiatric.

Agitation, anxiety, hallucinations, dream.

Gastrointestinal.

Nausea, vomiting, bowel distension following prolonged usage.

Haematological.

Severe megaloblastic anaemia, pancytopenia (observed in predisposing circumstances (cobalamin deficiency, substance abuse)), leucopenia/agranulocytosis (observed after very high and prolonged exposure for tetanus treatment in the 50's).

Eye disorders.

Severe visual impairment (caused by expansion of an intraocular gas, see Section 4.3 Contraindications; Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

Ear and labyrinth disorders.

Ear pain, middle ear disorders, tympanic rupture (in the event of obstruction of the eustachian tube - see Section 4.4 Special Warnings and Precautions for Use).

Metabolism and nutritional disorders.

Vitamin B₁₂ deficiency disorders (see Section 4.4 Special Warnings and Precautions for Use; Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

Pregnancy and lactation.

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

Retrolental fibroplasia.

Retrolental fibroplasia can occur in premature infants exposed to oxygen concentrations of greater than 40%.

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

Treatment.

There is no specific antidote. Treatment measures include: discontinuation of Nitronox, basic life support, assisted or controlled ventilatory support with oxygen and other symptomatic and supportive treatment.
Please consult the material safety data sheet for Nitronox from the sponsor.
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.

Nitrous oxide.

Nitrous oxide is an inhalational anaesthetic. The MAC (minimum alveolar concentration) in oxygen is greater than 100%.
Nitrous oxide has analgesic and weak anaesthetic properties. It has no dose related muscle relaxant effect. Onset and recovery from its effects are relatively rapid. Pain reduction may be achieved at a concentration of around 25%.
Nitrous oxide alone may increase pulse rate and have depressant effects on respiration.

Oxygen.

Oxygen comprises approximately 21% of atmospheric air and acts in the maintenance of various metabolic processes in the body.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption.

Nitrous oxide is rapidly absorbed via inhalation.
Oxygen is rapidly absorbed via inhalation, distributed mostly in combination with haemoglobin, consumed and exhaled along with carbon dioxide.

Distribution.

The alveolar concentration of N₂O rises rapidly due to its low blood:gas partition coefficient. Likewise, its elimination is very rapid.
The blood:gas partition coefficient of nitrous oxide at 37°C is 0.47 compared with that of nitrogen of 0.015, causing nitrous oxide to expand into internal gas spaces.

Metabolism.

The metabolism of nitrous oxide is minimal.

Excretion.

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

5.3 Preclinical Safety Data

Genotoxicity.

Nitrous oxide gave mixed results in limited assays for genotoxicity. In assays for gene mutations nitrous oxide was negative in the Ames test and sex-linked recessive lethal assay in Drosophila melanogaster, but was positive in Chinese hamster lung cells. The potential to cause chromosomal damage has not been investigated. 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, 1 day after 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.

Nitrous oxide was tested for carcinogenic potential in rats and mice. No carcinogenic effect was seen in mice exposed to nitrous oxide (40%, 4 hours per day) or rats exposed to low concentrations of halothane-nitrous oxide (10 ppm:500 ppm, 7 hours per day).

6 Pharmaceutical Particulars

6.1 List of Excipients

Nitronox does not contain any excipients.

6.2 Incompatibilities

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

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG).

6.4 Special Precautions for Storage

The normal precautions required in the storage and use of medicinal gas cylinders, are applicable. Please refer to Commonwealth, State and Territory Dangerous Goods legislation and the appropriate Australian Standards e.g. AS4332.
Cylinders should be stored:
away from sources of ignition, poisons, flammable or combustible materials;
preferably stored in an upright position in a secure area;
below 45°C and above 0°C in a dry well-ventilated area;
in an area constructed of non-combustible material with a firm level floor (preferably concrete);
away from heavy traffic and emergency exits;
out of the reach of children.
At temperatures below 0°C the nitrous oxide component may separate. Should this occur, or suspected to have occurred, cylinders must be stored in a horizontal position for at least 48 hours before their use, at a temperature of between 10°C and 30°C in a buffer zone inside the user department.

6.5 Nature and Contents of Container

Nitronox is supplied as a compressed gas in pressurized cylinders made of aluminium or steel and fitted with a pin index valve.
Cylinder colour: AS4484. Body colour - White AS2700; Shoulder colour - Ultramarine AS2700 and white quadrants.
Cylinder pressure: 12000 kPa (max) at 15°C.
See Table 1.
Not all cylinder sizes may be marketed.
Cylinders must be fitted with an appropriate pressure-reducing device (e.g. regulator).
Do not use Nitronox if the cylinder is damaged or has the tamper evident seal removed when in full storage.
When in use ensure Nitronox cylinders are:
Used only for medicinal purposes.
Moved using handing devices or trolley appropriate to the cylinder size.
Handled with care and not knocked violently or allowed to fall.
Secured to a suitable cylinder support when in use.
Not used in the vicinity of persons smoking or near naked lights or flames.
When empty ensure:
The cylinder valve is closed using only moderate force and the pressure in the regulator is released.
Replace valve caps where fitted.
Returned to the empty cylinder storage area.

Check the following before use.

Cylinders should not have been stored below 0°C. (See Section 6.4 Special Precautions for Storage.)
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.

Occupational exposure standard.

Worksafe exposure standard TLV TWA is 25 ppm.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements.

6.7 Physicochemical Properties

Chemical structure.

Nitrous oxide, N₂O is a linear but asymmetrical molecule of the form:

Oxygen has a molecular structure of:

Molecular weight: N₂O 44.01, oxygen 32.0.
Physical state in the cylinder: high pressure gas at ambient temperature.
Combustion characteristics: non-flammable, strongly supports combustion.

Chemical characteristics.

Nitrous oxide and oxygen are oxidising substances which will support combustion of materials which may not normally burn in air. Nitrous oxide is stable and comparatively unreactive at ordinary temperatures and pressures. 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 and other impurities, especially oil and grease may cause ignitions.

CAS number.

Nitrous oxide.

CAS number 10024-97-2.

Oxygen.

CAS number 7782-44-7.

7 Medicine Schedule (Poisons Standard)

(S4) Prescription Only Medicine.

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Consumer medicine information

Air Liquide Healthcare Nitronox 50% Nitrous Oxide and 50% Oxygen Mixture Gas Medicinal

Nitrous oxide; Oxygen

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