DONOPA

4). Paediatric population The success rate is lower in children under 3 years since the minimum effective alveolar concentration is higher than in older children. Method of administration Special precautions should be taken when working with nitrous oxide.

Nitrous oxide should be administered according to local guidelines. Donopa is administered via inhalation in spontaneously breathing patients via a face mask. Administration of Donopa is governed by the patient’s breathing. By holding the mask securely around the mouth and nose and breathing via the mask, a so-called “demand valve” is opened and Donopa flows out of the equipment and is administered to the patient via the airways.

Uptake occurs from the lungs. In dentistry, the use of a double mask is recommended, alternatively, a nasal mask or nasobuccal mask with adequate scavenging/ventilation is used. Administration via endotracheal tubes is not recommended.

If Donopa is to be used in patients breathing through an endotracheal tube, the administration should only be done by health care personnel skilled in the delivery of anaesthesia. Donopa should only be administered by personnel with knowledge of its use.

Administration of Donopa should only occur under supervision of, and with instruction from, personnel familiar with the equipment and its effects. Donopa should only be administered when the possibility of oxygen supplementation and equipment for resuscitation are readily available.

Ideally, the patient should hold the mask through which Donopa is administered. The patient should be instructed to hold the mask to his/her face and breathe normally. This is an additional safety measure to minimise the risk of overdose.

If for any reason the patient receives more Donopa than is necessary, and wakefulness becomes affected, the patient will drop the mask and administration will cease. By breathing ambient air, the effect of Donopa rapidly wears off and the patient will regain consciousness.

Donopa should preferably be used in patients capable of understanding and following instructions about how the equipment and the mask should be used. In children or in other patients that are not capable of understanding and following the instructions, Donopa might be administered under the supervision of competent medical personnel who can help them keep the mask in place and actively monitor the administration.

In such cases, Donopa may be administered with a constant gas flow. Due to the increased risk of the patient becoming markedly sedated and unconscious, this form of administration should, however, only take place under controlled conditions.

Continuous gas flow should only be used in the presence of competent personnel and with equipment available to manage the effects of the more pronounced sedation/decreased level of consciousness. The potential risk of possible inhibition of protective airway reflexes should be acknowledged and preparedness to secure the airway and assist ventilation available whenever constant flow is used.

When administration is ended the patient should be allowed to recover under calm and controlled conditions for around 5 minutes or until the patient’s degree of alertness/consciousness has recovered satisfactorily. Use in the treatment of short term pain conditions, during gynaecological and urological surgery and procedures, Administration of Donopa should commence shortly before the desired analgesic effect is required.

The analgesic effect is seen after 4-5 breaths and reaches its maximum within 2-3 minutes. Administration of Donopa should continue throughout the painful procedure, or for as long as the analgesic effect is desired. Following discontinuation of the administration/inhalation, the effects wear off quickly within a few minutes.

According to the individual pain relieving reaction in the patient, additional analgesics may be required. Use in odontics A nasal or oronasal mask may be used, depending on how the patient is ventilated. For disabled patients who are unable to keep the mask in place, it must be held by an operating nurse without strong physical constraint.

After a period of at least 3 minutes, the procedure may be performed, continuously if a nasal mask is used, or during periods of 20 to 30-second for the oronasal mask which may be pushed up on the nose during these periods. At the end of treatment, the mask is removed and the patient must left to rest in the chair for 5 minutes.

Use in obstetrics Inhalation should begin as soon as contraction starts. Women in labour must breathe normally during contraction and not hyperventilate because of the risk of oxygen desaturation between contractions. Inhalation must be discontinued after relief of pain.

Nitrous oxide should not be applied during pushing. Because of this risk of oxygen desaturation between contractions, the SaO2 must be continually monitored in this indication.

Megaloblastic anaemia and leukopenia have been reported following prolonged or repeated exposure to nitrous oxide. Neurological effects such as polyneuropathy and myelopathy have been reported with exceptionally high and frequent exposure.

However in patients with undiagnosed subclinical deficiency of vitamin B12, neurological toxicity has occurred after a single exposure to Nitrous Oxide for anaesthesia. Substitution treatment should be considered in all cases where vitamin B12 or folate deficiency may be suspected or where signs or symptoms of nitrous oxide-triggered effects on methionine synthesis have arisen.

The table shows the adverse drug reactions associated with Donopa. Frequencies are defined as: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1000 to <1/100); rare (≥1/10000 to <1/1000); very rare (<1/10000; including isolated reports), not known (cannot be estimated from the available data).

System Organ Class Frequency Adverse reaction Blood and lymphatic system disorders Not known Megaloblastic anaemia, leukopenia. Psychiatric disorders Not known Psychosis, confusion anxiety. Addiction. Common Dizziness, light-headedness, euphoria.

Nervous system disorders Uncommon Severe fatigue. Not known Polyneuropathy, paraparesis and myelopathy, respiratory depression, headache, abnormal movements have sometimes been observed in particular against a background of hyperventilation, myeloneuropathy, Neuropathy, Subacute degeneration of the spinal cord.

Generalised seizures. Ear and labyrinth disorders Uncommon Feeling of pressure in the middle ear. Gastrointestinal disorders Uncommon Bloating, increased volume of gas in the intestines. Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important.

It allows continued monitoring of the benefit/risk balance of the medicinal product. uk/yellowcard

Donopa should only be administered by competent personnel with access to adequate resuscitation equipment. 2) Repeated administration or exposure to nitrous oxide may lead to addiction. Caution should be excercised in patients with a known history of substance abuse or in healthcare professionals with occupational exposure to nitrous oxide.

g. regurgitation and aspiration, should be considered. Warnings 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.

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. Areas in which Donopa is used should be adequately ventilated and/or equipped with scavenging equipment in order that the concentration of nitrous oxide in ambient air is below set national hygienic limit values; according to TWA (time weight average), the mean value over a working day and STEL (short term exposure limit) mean value during shorter exposure, national set values must always be followed.

The gas mixture should be stored and used only in areas/rooms where the temperature exceeds 0
C. At lower temperatures the gas mixture can separate and result in administration of a hypoxic gas mixture. Paediatric population Donopa can be used in children that are able to follow instructions on how to use the equipment.

In the treatment of younger children, or in other patients that are not capable of following instructions, the use of constant gas flow may be required. Constant gas-flow should only be provided by healthcare personnel trained in use of the gas, with equipment available to secure the airway and for provision of assisted ventilation.

) Use of Donopa is not recommended in neonates. Nitrous oxide may cause in rare cases respiratory depression in the neonate. The neonate should be checked for possible respiratory depression when Donopa is used during childbirth. Precautions for use Avoid hyperventilation as this may cause abnormal movements.

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 subacute combined degeneration of the spinal cord.

Nitrous oxide should not be used 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 vitamin B12 levels in the normal range. In patients with undiagnosed subclincial deficiency of vitamin B12, neurological toxicity has occured after single exposures to Nitrous Oxide during anaesthesia.

Due to its nitrous oxide content, Donopa can increase pressure in the middle ear and other air-filled cavities. g. morphine derivatives and/or benzodiazepines, concomitant administration of Donopa may result in increased sedation, and consequently have effects on respiration, circulation and protective reflexes.

If Donopa is to be used in such patients, this should take place under the supervision of appropriately trained personnel. 5) Following discontinuation of administration of Donopa, the patient should be advised to recover under proper supervision until these potential risks resulting from use of Donopa have subsided and the patient has recovered satisfactorily.

Recovery of the patient should be assessed by health care personnel. After cessation of Donopa 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.

This can be prevented by oxygen supplementation. Nitrous oxide exerts synergistic effects on folate metabolism when administered with methotrexate (MTX), and this may impair tolerability to MTX. Alternative treatment options for nitrous oxide may be considered in patients using MTX.

When Donopa is inhaled, gas bubbles (gas emboli) and gas-filled cavities may expand due to the increased ability of nitrous oxide to diffuse. Consequently, Donopa is contraindicated in the following conditions: - In patients with signs or symptoms of pneumothorax, pneumopericardium, severe emphysema, gas emboli or head injury.

- Following deep sea diving with risk of decompression sickness (bubbles of nitrogen). - Following cardiopulmonary bypass with heart lung machine or coronary bypass without heart lung machine. g. SF6, C3F8) until the gas in question is fully absorbed, because the gas volume may increase in pressure/volume and consequently result in blindness.

- In patients with a severely dilated gastrointestinal tract. g. after cardiac surgery) in order to avoid the risk of further deterioration in heart function. - In patients presenting signs of confusion or in some other way showing signs of increased intracranial pressure.

- In patients with a decreased level of consciousness or impaired ability to cooperate and follow instructions due to the risk that further sedation from the nitrous oxide may affect natural protective reflexes. - In patients with diagnosed but untreated vitamin B12- or folic acid deficiency (including in early pregnancy) or diagnosed genetic disorder of the enzyme system involved in metabolism of these vitamins.

- In patients with facial injury where use of a facemask may present difficulties or risks.