Donopa

Package leaflet: Information for the user

DONOPA 50%/50% v/v medicinal compressed gas

Nitrous oxide / oxygen
Please read all of this leaflet carefully before you use this medicine because it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, talk to your doctor or pharmacist. See section 4.

Contents of this leaflet

1. What Donopa is and what it is used for
2. What you need to know before using Donopa
3. How to use Donopa
4. Possible side effects
5. How to store Donopa
6. Contents of the pack and other information

1. What Donopa is and what it is used for

Donopa contains a ready-made mixture of nitrous oxide (N₂O) and oxygen (medicinal oxygen, O₂), each at 50%, and is intended for inhalation of the mixture.
Donopa can be used in adults and children over 1 month of age.
Effects of Donopa
Nitrous oxide constitutes 50% of the gas mixture. Nitrous oxide has an analgesic effect, reduces the sensation of pain, and increases the pain threshold. Nitrous oxide also has a relaxing and mildly sedative effect. These effects result from the action of nitrous oxide on signal-transmitting substances in the nervous system.
The effect of Donopa is reduced in children under three years of age.
The 50% oxygen concentration, approximately double that of ambient air, ensures a safe oxygen content in the inhaled gas.
Donopa should be used

• when a rapidly acting and rapidly reversible analgesic effect is desired, and when the pain to be treated is of mild to moderate intensity and short duration. Donopa produces analgesic effects after a few breaths, and analgesic effects diminish within a few minutes after discontinuation.
• for dental surgery in anxious patients.

2. What you need to know before using Donopa

Do not use Donopa:
Before using Donopa, inform your doctor if any of the following signs/symptoms occur:

• Gas-filled cavities or gas bubbles: when, due to illness or for any other reason, there is suspicion of air in the chest cavity outside the lungs, or gas bubbles in the blood or in an organ. For example, during scuba diving, gas bubbles may be present in the blood, or during a procedure involving injection of gas into the eye, such as for retinal detachment or other conditions. These gas bubbles may expand and become dangerous.
• Heart disease: in case of heart failure or severely impaired cardiac function, as the slight relaxing effect of nitrous oxide on heart muscle may further worsen heart failure.
• Central nervous system disorders: in case of increased intracranial pressure, for example due to a brain tumor or cerebral hemorrhage, since nitrous oxide may further increase intracranial pressure and potentially be dangerous.
• Vitamin deficiency: in case of diagnosed deficiency of vitamin B₁₂ or untreated folic acid deficiency (including early pregnancy), as the use of nitrous oxide may worsen symptoms caused by vitamin B₁₂ and folic acid deficiency.
• Ileus (intestinal obstruction): in case of severe abdominal pain; if symptoms suggest intestinal obstruction, as the use of Donopa may further increase intestinal distension.

Warnings and precautions
Talk to your doctor or pharmacist before using Donopa if:

• You are or have been misusing medicines, as repeated administration of nitrous oxide may increase the risk of developing dependence. Your doctor will determine whether treatment with Donopa is appropriate in your case.

Repeated or prolonged use of nitrous oxide may increase the risk of vitamin B₁₂ deficiency, which can cause damage to the bone marrow and nervous system. Your doctor may initiate hematological monitoring before and after treatment to assess the consequences of possible vitamin B₁₂ deficiency.
Additionally, inform your doctor if any of the following signs/symptoms occur:

• Ear problems: for example, ear inflammation, as Donopa may increase pressure in the middle ear.
• Vitamin deficiency: in case of suspected deficiency of vitamin B or folic acid, as the use of nitrous oxide may worsen symptoms caused by vitamin B and folic acid deficiency.
• Success rates are lower in children under 3 years of age.

You must breathe normally during inhalation.
Your doctor will decide whether Donopa is suitable for use.

Other medicines and Donopa
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
If you are taking other medicines that affect the brain or brain function, for example benzodiazepines (tranquilizers) or morphine-like medicines, inform your doctor. Donopa may enhance the effects of these medicines. The use of Donopa in combination with other sedatives or other medicines acting on the central nervous system increases the risk of adverse effects.
Also inform your doctor if you are taking medicines containing methotrexate (e.g., for the treatment of rheumatoid arthritis), bleomycin (for cancer treatment), nitrofurantoin or similar antibiotics (for treating infections), or amiodarone (for treating heart diseases). Donopa increases the adverse effects of these medicines.

Pregnancy, breastfeeding and fertility
Donopa may be used during pregnancy if clinically necessary.
After a short administration of Donopa, it is not necessary to interrupt breastfeeding.
If you are pregnant, breastfeeding, suspect you may be pregnant, or are planning to become pregnant, consult your doctor or pharmacist before using this medicine.

Driving and using machines
If you have been administered Donopa without additional sedative/analgesic medicines, for safety reasons avoid driving, operating machinery, or performing complex tasks until you have fully recovered (at least 30 minutes).
Ask your doctor whether it is safe for you to drive.

3. How to use Donopa

Donopa will always be administered to you under the supervision of personnel experienced in the use of this type of medicine. This ensures that the administration of Donopa is appropriate for you and that the equipment has been correctly prepared. During Donopa administration, you will be monitored to ensure safe use. After Donopa administration, you will continue to be monitored by qualified personnel until you have fully recovered.

You must always use this medicine exactly as instructed by your doctor.
Your doctor will explain to you how to use Donopa, how it works, and what effects to expect. If you have any doubts, consult your doctor.

Donopa is generally inhaled through a mask attached to a special valve that allows complete control of gas flow through your breathing. The valve opens only during inhalation. Donopa may also be administered through a so-called nasal mask.

Regardless of the type of mask used, you must breathe normally through the mask.
After stopping the use of Donopa, you should rest until you feel you have fully regained mental control.

Safety precautions

• Smoking and lighting flames are strictly prohibited in the rooms where Donopa treatment takes place.
• Donopa is intended exclusively for medical use.

If you use more Donopa than you should
It is very unlikely that you will be given too much gas, as you yourself control the administration of the gas. In addition, the gas mixture is fixed (containing 50% nitrous oxide and 50% oxygen).
If you breathe faster than normal, the amount of nitrous oxide administered will be higher than if you were breathing normally, and you may feel tired or somewhat detached. In this case, you must immediately inform the medical staff and stop the administration.
If you have any doubts about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Common (may affect up to 1 in 10 people)
Dizziness, feeling faint, euphoria, nausea and vomiting
Uncommon (may affect up to 1 in 100 people)
Severe fatigue. Feeling of pressure in the middle ear if Donopa is used for a prolonged period.
This occurs because Donopa increases the pressure in the middle ear.
Abdominal bloating, because Donopa slightly increases the volume of intestinal gas.
Not known (frequency cannot be estimated from the available data)
Effects on bone marrow leading to anaemia.
Effects on nerve function, sensation of numbness and weakness, usually in the legs.
This is because nitrous oxide affects vitamin B and folate metabolism, inhibiting an enzyme: methionine synthase.
Abnormal movements may occur after hyperventilation (increased respiratory rate during inhalation).
Respiratory depression. Occasionally headache.
Psychiatric effects, such as psychosis, confusion, anxiety, dependence.
Generalized epileptic seizures.

Reporting of adverse reactions
If you experience any adverse reaction, including those not listed in this leaflet, consult your doctor or pharmacist.
You may also report adverse reactions directly via the website https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting adverse reactions, you can help provide more information on the safety of this medicine.

5. How to store Donopa

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the batch label of the cylinder. The expiry date refers to the last day of that month.
Store between 0 °C and 50 °C. Do not freeze.
If it is suspected that Donopa has been stored at an excessively low temperature, the cylinders must be kept horizontally at a temperature above +10 °C for at least 48 hours before use.
Keep away from combustible materials.
Contact with combustible materials may cause fires.
Do not smoke or use open flames near Donopa.
Do not expose to excessive heat.
In case of fire risk, move the cylinder to a safe place.
The cylinder must be kept clean, dry, and free from oils and greases.
Store the cylinder in a closed area designated exclusively for the storage of medicinal gases.
During storage and transport, the valves must be closed.
Ensure that the cylinder is not subjected to impact or dropped.
Inhalation of vapours may cause drowsiness and dizziness.

6. Package contents and other information

What Donopa contains

• The active substances are: nitrous oxide 50% (v/v) (chemical formula: N₂O) and oxygen 50% (v/v) = medicinal oxygen (chemical formula: O₂)
• Donopa does not contain any other components

Description of the appearance of Donopa and contents of the package
Donopa is a colourless, odourless and tasteless gas supplied in a cylinder with a valve for controlling gas flow.
The cylinder may be made of steel or aluminium.
The shoulder of the cylinder is marked with white and blue (oxygen/nitrous oxide). The body of the cylinder is white (medicinal gas).
Pharmaceutical form: compressed medicinal gas

Contents in litres (135 bar): 2, 2.7, 5, 10, 15, 20
Contents in litres (185 bar): 2, 5
Not all pack sizes may be marketed.

Marketing Authorisation Holder
SOL SpA
Via Borgazzi, 27
20900 Monza
Italy

Manufacturer
SOL France
ZI les Bethunes
8 Rue du Compas
95310 Saint Ouen l’Aumone
France

This medicinal product is authorised in the European Economic Area countries under the following names:
Austria: Donopa
Belgium: Antafil, 50%/50% v/v, gaz médicinal comprimé
Bulgaria: Donopa
Croatia: Donopa
Germany: Donopa
Greece: Donopa
Hungary: Donopa
Ireland: Donopa
Italy: Donopa
Luxembourg: Antafil, 50%/50% v/v, gaz médicinal comprimé
Netherlands: Donopa
Slovenia: Donopa
Spain: Donopa
UK: Donopa

The following information is intended exclusively for healthcare professionals:

Safety precautions
Repeated administration or exposure to nitrous oxide may lead to dependence.
Healthcare professionals with occupational exposure to nitrous oxide should exercise caution.
Nitrous oxide must be administered in accordance with local guidelines.
Donopa should only be used in well-ventilated areas equipped with special equipment for evacuation of excess gas. The use of a scavenging system and ensuring adequate ventilation help prevent high concentrations of nitrous oxide in the ambient air.
Elevated concentrations of nitrous oxide in ambient air may cause adverse health effects in personnel or others nearby. National guidelines exist for the maximum allowable concentration of nitrous oxide in ambient air—the so-called "occupational exposure limits," frequently expressed as TWA (time-weighted average), i.e., average exposure over a working day, and STEL (short-term exposure limit), i.e., average exposure over a shorter period.
These values must not be exceeded to ensure personnel are not exposed to risks.

• The valve must be opened slowly and carefully.
• In case of fire or when not in use, deactivate the equipment.
• During use, the gas cylinder must be securely fastened and placed in an appropriate support.
• Replace the gas cylinder when the internal pressure drops to the point where the indicator on the valve enters the yellow zone.
• If a small residual amount of gas remains in the cylinder, the valve must remain closed. It is important that residual pressure remains inside the cylinder to prevent entry of contaminating substances.
• After use, close the cylinder valve by hand. Depressurize the regulator or connection.