Prospect: information for the user

KALINOX 50%/50%,compressed medicinal gas in ampoules

Nitrous oxide / Oxygen

Read this prospect carefully before starting to use this medication, because it contains important information for you.

Conserve this prospect, as you may need to read it again.

• If you have any doubts, consult your doctor, or pharmacist or nurse.
• This medication has been prescribed only to you, and you must not give it to other people, even if they have the same symptoms as you, as it may harm them.
• If you experience adverse effects, consult your doctor, or pharmacist or nurse, even if they are not listed in this prospect. See section 4

1. What is KALINOX and how it is used

2. What you need to know before starting to use KALINOX

3. How to use KALINOX

4. Possible adverse effects

5. Conservation of KALINOX

6. Contents of the package and additional information

KALINOXis a mixture of two medicinal gases (nitrous oxide 50% and oxygen 50%). It belongs to the group of analgesics (medicines that relieve pain).

At this concentrationKALINOXhas no anesthetic effects.

KALINOXis indicated for painful short-duration operations.

No use KALINOXin the following cases

• Any change in the level of consciousness that prevents the patient from cooperating.
• Patients who require pure oxygen ventilation
• Head injuries
• Pneumothorax (Accumulation of air or gas in the pleural cavity)
• Bullous emphysema (Destruction of lung tissue by the presence of air)
• Gas embolism (Obstruction of a vessel by the presence of air or gas bubbles)
• Decompression sickness
• After recent underwater immersion
• After an air encephalogram
• Abdominal gas distension
• Maxillofacial trauma affecting the area of application of the mask
• During ear, middle ear, and nasal sinus surgery
• If air has been injected into the epidural space to determine the placement of the epidural anesthesia needle
• Patients who have recently received an intraocular injection of gas (such as SF6, C3F8, CsF6) as long as an intraocular gas bubble persists or within 3 months after the last intraocular gas injection. The expansion of an intraocular gas bubble by nitrous oxide can cause severe visual deterioration

The use ofKALINOXmust be stopped immediately in case of loss of verbal contact.

Warnings and precautions:

• The gas must be administered by adequately trained personnel. You should never transport KALINOX cartridges.
• Rooms where KALINOX is used must be equipped with an air conditioning system or an adequate ventilation system to maintain the nitrous oxide levels in the ambient air to a minimum.
• Breathe normally during gas inhalation.
• Before administering KALINOX, do not apply greasy substances (creams, ointments, etc.) to the face.
• The success rate of the treatment is lower in children under 3 years old.
• Nitrous oxide causes the inactivation of vitamin B12 (a cofactor of methionine synthase) that interferes with folate metabolism. Consider evaluating vitamin B12 levels in patients with risk factors for vitamin B12 deficiency before using nitrous oxide anesthesia. Risk factors may include patients with anemia or gastric atrophy, those on a vegetarian diet, or who have used medication that may interfere with vitamin B12 and/or folate metabolism. Vitamin B12 supplements should be given in case of repeated or prolonged administration.
• In case of Eustachian tube obstruction, due to increased pressure in the middle ear cavity, ear pain and/or tympanic membrane rupture may be observed.
• Abuse, misuse, and diversion: due to the euphoric effects of nitrous oxide, it may be sought and become the subject of recreational abuse.
• Intracranial pressure must be closely monitored in patients diagnosed with or at risk of intracranial hypertension, as an increase in intracranial pressure has been observed during nitrous oxide administration in some patients with intracranial disorders.

Use of KALINOX with other medications

Inform your doctor if you are using or have recently used other medications, including those obtained without a prescription.

• If you have been treated with ocular gases (SF6, C2F6, C3F8) in ophthalmic surgery (eye surgery), always inform your doctor so that he/she can ensure that administration does not expose you to post-operative complications that may cause increased pressure inside the eye.
• In combination with medications acting on the central nervous system (such as morphine derivatives, benzodiazepines, and other psychotropic medications), the risk of somnolence, desaturation (reduction of oxygen in the blood), vomiting, and hypotension increases. In case of association with this type of medication, patient vigilance must be reinforced.
• Medications that interfere with vitamin B12 and/or folate metabolism may potentiate the inactivation of vitamin B12 by nitrous oxide.

Pregnancy and lactation

Consult your doctor or pharmacist before using any medication.

• Use of KALINOX is not recommended during the first trimester of pregnancy. Nitrous oxide may be used during pregnancy if clinically necessary. When nitrous oxide is used near birth, newborns must be monitored for possible adverse effects.
• There have been reports of an increase in spontaneous abortions and malformations in women exposed to chronic occupational inhalation of nitrous oxide during pregnancy, in the absence of an adequate ventilation system.

Driving and operating machinery

After administration, do not drive or operate machinery until all side effects have disappeared and normal consciousness is restored.

Follow exactly the administration instructions of this medication as indicated by your doctor. Consult your doctor if you have any doubts.

The administration must be performed in adapted locations, by specialized doctors or nurses specifically trained, in charge of continuous patient monitoring.

The duration of the inhalation of the mixture depends on the duration of the corresponding operation and should not exceed 60 minutes consecutive. In case of daily administration, it should not exceed 15 consecutive days. After suspension of the inhalation, the return to the initial situation is almost immediate and without residual effect.

The flow of the mixture (amount of gas received per second or per minute) is determined by the patient's spontaneous ventilation.

Use in painful operations:

Before performing the operation, the mask should be kept for 3 minutes. During this time interval, verbal contact with the patient is maintained. The person monitoring the administration gives consent to start the operation. The inhalation of the gas is maintained throughout the operation, indicating to the patient to breathe normally.

During administration, clinical vigilance is essential. The patient must be relaxed, breathe normally, and respond to simple orders. In case of intense sedation, with loss of verbal contact, the mask will be removed until verbal contact is restored.

Use in dentistry:

In patients whose disability prevents them from keeping the mask correctly placed, it will be held by another person without exerting much pressure. After 3 minutes, the operation can be performed uninterruptedly, if a nasal mask is used, or during periods of 20 to 30 seconds, if a buconasal mask (which covers the nose and mouth) is used, which, in these cases, will be raised above the nose during the mentioned periods.

At the end of the operation, the mask will be removed and the patient will remain at rest in the dental chair for 5 minutes.

Use in obstetrics (pregnancy, childbirth, and postpartum):

The inhalation of the gas should start from the beginning of contractions, before the pain appears. The parturient should breathe normally during the contraction and avoid hyperventilating (breathing rapidly or deeply that produces a sensation of lack of air) due to the risk of oxygen desaturation (reduction of oxygen level in blood) between contractions. The inhalation of the gas will be interrupted from the moment the pain decreases. In this indication, it is recommended to continuously monitor the oxygen level.

If you use more KALINOX than you should

If you have used moreKALINOX thanyou should, consult your doctor immediately or call the Toxicological Information Service, phone 91- 562 0420, indicating the medication and the amount.

In case of inadequate storage, at a temperature below 0º C,cyanosis (lack of oxygen) may occur. In this case, both gases (nitrous oxide and oxygen) may come out separately from the container.

If cyanosis appears during administration, immediate suspension of treatment is mandatory; if, despite this, cyanosis does not disappear quickly, it will be necessary to ventilate the patient with a manual balloon filled with ambient air.

Overdose may cause an increase in dizziness, unconsciousness, cyanosis, and death due to anoxia.

Under these circumstances, treatment should be stopped immediately and the necessary measures should be taken.

Like all medications,KALINOXmay cause adverse effects, although not all people will experience them.

Nitrous oxide diffuses into all gas-filled spaces faster than nitrogen. The use of nitrous oxide may lead to the expansion of gas-filled cavities without ventilation.

Frequent (> 1/100 to <1)

Gastrointestinal disturbances: Nausea, vomiting

Rare (> 1/1,000 to <1)

Nervous system disturbances: Paresthesia. Excessive sedation.

Psychiatric disorders: Euphoria, agitation, anxiety, hallucinations, nightmares

Unknown (cannot be estimated from available data):

Nervous system disorders: Dizziness, myelopathy, neuropathy, increased intracranial pressure, generalized seizures.

Blood and lymphatic system disorders: Megaloblastic anemia, pancitopenia (observed in susceptible circumstances (cobalamin deficiency, substance abuse)), leucopenia/agranulocytosis (observed after high and prolonged exposure to tetanus treatment in the 1950s)

Eye disorders: Severe visual impairment (caused by the expansion of an intraocular gas.

Ear and labyrinth disorders: Ear pain, middle ear disorders, eardrum rupture (in case of Eustachian tube obstruction).

Respiratory, thoracic, and mediastinal disorders: Respiratory depression (in the newborn, when nitrous oxide is used during delivery.

Metabolic and nutritional disorders: Vitamin B12deficiency.

Psychiatric disorders: Disorientation

Reporting Adverse Effects

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect not listed in this prospectus. You can also report it directly through the Spanish System for Pharmacovigilance of Medicinal Products for Human Use:www.notificaRAM.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medication.

Keep out of sight and reach of children.

Filled cartridges must be stored IN A HORIZONTAL POSITION, between 10 and 30°C, at least 48 hours before use, with valves closed.

Protect cartridges from impacts, falls, heat sources or ignition, combustible materials, inclement weather, and, in particular, cold temperatures.

Do not use KALINOXafter the expiration date appearing on the packaging after “CAD”. The expiration date is the last day of the month indicated.

All guidelines for handling pressure containers must be followed.

Composition of KALINOX

• The active principles are: nitrous oxide and oxygen. Each cartridge contains a mixture of both components at 50% (mol/mol).
• It does not contain other components (excipients).

Appearance of the product and contents of the packaging

KALINOXis packaged in cartridges, available in the following sizes:

Legend of valve type:

1Package available with valve without integrated pressure regulator (Standard RPV valves).

2Package available with valve with integrated pressure regulator (Compact G2 (Compact) valves).

3Package available with valve with integrated pressure regulator (M706 (One K) valves).

Some package sizes may only be commercially available.

Marketing authorization holder and responsible manufacturer

Marketing authorization holder:

AIR LIQUIDE Santé INTERNATIONAL

75, Quai D`Orsay

75007 - Paris (France)

Responsible manufacturer:

AIR LIQUIDE MEDICAL

Tolhuisstraat 46-48

2627 - Schelle (Belgium)

AIR LIQUIDE Santé FRANCE

Les petits carreaux

2, avenue du Lys

94380 Bonneuil sur Marne

France

Last review date of this leaflet:June 2024

Instructions for use and handling

KALINOXis reserved for hospital use.

The oxygen concentration (FiO2) must never be less than 21%.

To avoid accidents, the following instructions will be respected:

• The personnel handling the cartridges must be trained in the use of gases.
• Do not use any suspicious cartridge that has been exposed to a temperature below 0°C.
• In case of observing frost on the cartridge, do not use it and return it.
• Do not handle a cartridge whose valve is not protected by a tulip.
• Do not use a cartridge that has leaks.
• Do not lift the cartridge by its valve.
• Do not attempt to repair a faulty valve.
• Hold the cartridges with an appropriate means (chains, hooks, etc.), in order to keep them inVERTICAL POSITIONand prevent falls.
• Do not force the placement of a cartridge in a support where it enters with difficulty.
• Ventilate the place of use properly. In case of prolonged use, accident, or unexpected leak, ensure the possibility of evacuating the gases. The Mean Exposure Limit Value of nitrous oxide has been established at 50 ppm with regard to the exposure of personnel.
• Do not position yourself in front of the valve outlet, but on the opposite side of the flowmeter, behind the cartridge and at a certain distance. Do not expose the patient, in any case, to the gas flow.
• Handle the material with clean and grease-free hands.
• Do not use aerosol generators (lacquer, deodorant, etc.), or solvents (alcohol, gasoline, etc.) on the material or in its vicinity.

• Do not apply greasy substances (vaseline, ointments, etc.) to the patients' faces.

• Do not grease.
• Do not smoke.
• Do not approach a flame.

And in particular:

a)Never introduce this gas into an apparatus that could be suspected of containing combustible substances, especially greases

b) Do not clean with combustible products, especially greasy materials, the apparatus containing this gas, valves, joints, closure devices, and circuits.

In case of leak, close the valve presenting the leak. Ventilate the area intensively and evacuate it.

In case of fire, the risk of toxicity increases due to the formation of nitrous vapors.

In the case of cartridges equipped with a valve:

• Open the valves of the cartridges slightly before connecting the pressure regulator to remove any particles or foreign matter. Keep the contact point between the cartridge and the pressure regulator clean at all times.
• The cartridges are equipped with a flowmeter: They have a specific connection for the nitrous oxide-oxygen medical mixture, in accordance with the NF S 90-116 standard.
• Use a pressure regulator with a flowmeter capable of reading pressures of at least 1.5 times the maximum working pressure of the cartridge.

To open the cartridge after connection:

• Follow the instructions on the cartridge label.
• Never force the valve when opening it, or open it fully.
• Always open the valve slowly to avoid cooling, which can cause the mixture to become heterogeneous.
• Never pressurize the pressure regulator repeatedly.
• Do not transfer gas from a low-pressure cartridge to another cartridge.

After use:

• Closing the valve of the cartridge after use and allowing the pressure regulator to read the flowmeter, then closing the flowmeter and loosening the adjustment screw of the pressure regulator.
• Never empty a cartridge completely and always leave it at a minimum pressure of 10 bar.

Keep the empty cartridges inVERTICAL POSITION, with the valves closed (to prevent corrosion due to humidity).