NITRONOX INHALATION GAS

Nitronox is for inhalation use. Posology In nearly all cases, Nitronox is self-administered, but it may be administered by attendant medical personnel. Doses may be self-regulated by the use of a face mask or mouthpiece connected through a demand valve to the Nitronox cylinder.

Since pain is usually relieved by a concentration of 25% nitrous oxide, continued inhalation does not occur. However, should inhalation continue, light anaesthesia occurs and the mask or mouthpiece drops away as the patient relaxes, or is removed if administration has been by attendant personnel.

8). Paediatric population As for adults Method of administration Nitronox is administered through a face mask or mouthpiece. The face mask or mouthpiece is connected to a Nitronox supply through a demand valve system which allows the Nitronox to be self-regulated by the patient.

The valve is operated by the act of inhalation of the patient and closes down when the patient ceases to inhale. Nitronox may be administered by personnel trained in its use (obstetric units, accident units and accident ambulances).

6.

Summary of the safety profile Events such as euphoria, disorientation, sedation, nausea, vomiting, dizziness and general tingling are commonly described. These events are generally minor and rapidly reversible. Addiction may occur. 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. 4). 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. Tabulated list of adverse reactions Adverse reaction frequencies are defined using the following convention: Very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1000 to <1/100), rare (≥1/10,000 to <1/1000), very rare (<1/10,000) and not known (cannot be estimated from the available data).

System Organ Class Frequency Adverse Event Blood and lymphatic system disorders Not known Megaloblastic anaemia, agranulocytosis Common Euphoria, sedation, disorientation Psychiatric disorders Not known Addiction, confusion Common Dizziness, tingling, light-headedness Uncommon Somnolence Nervous system disorders Not known Generalised seizures, myeloneuropathy, neuropathy, subacute degeneration of the spinal cord Uncommon Feeling of pressure in the middle ear Ear and labyrinth disorders Not known Middle ear damage, perforated ear drums Common Nausea, vomiting Uncommon Bloating, increased gas volume in the intestines Gastrointestinal disorders Not known Abdominal distension General disorders and administration site conditions Common Sense of intoxication Respiratory, thoracic and mediastinal disorders Not known Respiratory depression Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important.

Repeated administration or exposure to nitrous oxide may lead to addiction. Caution should be exercised in patients with a known history of substance abuse or in healthcare professionals with occupational exposure to nitrous oxide. 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 administration of nitrous oxide. 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 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 anaesthesia. Reduced fertility in healthcare personnel has been reported where they have been repeatedly exposed to levels of nitrous oxide above the specified occupational exposure limits in inadequately ventilated rooms.

There is no documented evidence to confirm or exclude the existence of any causal connection between these cases and exposure to nitrous oxide. In patients taking other centrally acting depressant medicinal products, such as morphine derivatives and/or benzodiazepines, concomitant administration of Nitronox may result in increased sedation, and consequently have effects on respiration, circulation and protective reflexes.

Hypersensitivity to nitrous oxide. 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 • patients that have received recent intraocular injection of gas (such as SF6)