Glutathione, Mannitol, Lactobionic acid, Glutamic acid, Sodium hydroxide
Calcium chloride dihydrate, Potassium chloride, Magnesium chloride hexahydrate, Histidine
Please read this leaflet carefully before using this medicine because it contains
important information for you.

Keep this leaflet. You may need to read it again.
If you have any questions, consult your doctor or pharmacist.
If you experience any adverse reactions, including those not listed in this leaflet, consult your doctor or pharmacist. See section 4.

Contents of this leaflet:

What Celsior is and what it is used for
What you need to know before using Celsior
How to use Celsior
Possible side effects
How to store Celsior
Contents of the pack and other information

1. What Celsior is and what it is used for

Pharmacotherapeutic category: solvents and diluents, including washing solutions.
Solution for organ preservation of thoracic organs (heart and lungs) and abdominal organs (kidney, liver and pancreas) during transplantation: from removal from the donor, as well as during storage, transport, and until transplantation into the recipient.

2. What you need to know before using Celsior

Do not use Celsior
Celsior must not be used for organ preservation if the donor or the recipient is
allergic (hypersensitive) to the active substances or to any of the other ingredients of this
medicinal product (listed in section 6).
Warnings and precautions
Celsior is not suitable for direct injection or intravenous use in the organ recipient;
therefore, it must be used solely for flushing and cold storage of solid organs.
Celsior is for single use only. It is not suitable for use in machines that continuously pump the preservation solution through the organ (mimicking blood circulation).

Other medicines and Celsior
There are no known interactions when used as directed.
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, planning a pregnancy, or breastfeeding,
consult your doctor or pharmacist before using this medicinal product.
No data are available. Since Celsior is not administered systemically to organ recipients,
specific effects of the solution are not expected.

3. How to use Celsior

Celsior may only be used by appropriately trained medical personnel as described in the section: The following information is intended exclusively for physicians or healthcare professionals.
Once removed from the donor and before transplantation into the recipient, the organ receives neither blood nor oxygen; therefore, it must be preserved at a temperature of 2–8°C in order to ensure proper function in the recipient. Organs are usually flushed to remove blood and to cool them, thereby slowing down metabolism. The organ is immediately placed in a sterile container filled with Celsior and kept cool, without being frozen.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Since Celsior is not administered to organ recipient subjects, no specific adverse reactions related to the solution are expected. However, you must immediately report any adverse reactions, including those known to be associated with other medicines taken during the transplant procedure, so that appropriate precautions can be evaluated.
An abnormal heart rate or low blood pressure may occur. Patients receiving a heart transplant may experience abnormal cardiac function. Exceeding the recommended volume of solution may lead to increased body fluids and abnormal levels of body salts.

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, please inform your doctor or nurse. You may also report side effects directly via
http://www.agenziafarmaco.gov.it/it/responsabili . By reporting side effects, you can help provide further information on the safety of this medicine.

5. How to store Celsior

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the bag and carton after EXP. The expiry date refers to the last day of that month.
To protect from light, keep in the original aluminium packaging. Store and transport in a refrigerator (2°C - 8°C). Do not freeze.
After opening, Celsior must be used within 24 hours.
Do not use this medicine if you notice any particles, or if the solution is not clear, colourless, or has a slightly yellow colour.
Do not dispose of medicines via wastewater. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Celsior contains
The active substances are: glutathione, mannitol, lactobionic acid, glutamic acid, sodium
hydroxide, calcium chloride dihydrate, potassium chloride, magnesium chloride hexahydrate, histidine.
Each 1-litre bag of solution contains:
Glutathione 0.921 g 3 mmol
Mannitol 10.930 g 60 mmol
Lactobionic acid 28.664 g 80 mmol
Glutamic acid 2.942 g 20 mmol
Sodium hydroxide 4.000 g 100 mmol
Calcium chloride dihydrate 0.037 g 0.25 mmol
Potassium chloride 1.118 g 15 mmol
Magnesium chloride hexahydrate 2.642 g 13 mmol
Histidine 4.650 g 30 mmol

The other components are:
Water for injections
Sodium hydroxide, 4% (for pH adjustment)

Description of the appearance of Celsior and contents of the pack
Organ preservation solution
Celsior is a clear, colourless (or slightly yellow) solution contained in a bag made of ethylene
vinyl acetate copolymer, enclosed in an outer aluminium packaging containing an oxygen absorber.
pH = 7.3
Osmolality: 320 mosmol/kg
Multiple packs of 4 bags, each containing 1 litre of solution.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Institut Georges Lopez – IGL
1 allée des Chevreuils – Route Nationale 6
Parc tertiaire du Bois Dieu
69380 Lissieu
France
Tel: 00.800.1212.5656

Manufacturer
6 route de Saint Bonnet
69930 Saint-Laurent-de-Chamousset
France

This medicinal product is authorised in the European Economic Area Member States under the
following names:
Austria Celsior Organkonservierungslösung
Germany Celsior Organkonservierungslösung
France Celsior solution pour conservation d’organes
Ireland Celsior Solution for organ preservation
Italy Celsior soluzione per conservazione di organi
Portugal Celsior solução para conservação de órgãos
Spain Celsior solución para la conservación de órganos

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The following information is intended exclusively for physicians or healthcare professionals:
Special warnings and precautions for use
Celsior is not suitable for direct injection or intravenous use in the recipient and must therefore be used solely for cold flushing and storage of solid organs.
Celsior is for single use only. Do not reuse. It is not suitable for continuous mechanical perfusion.
It cannot be excluded that residual amounts of the solution may lead to arrhythmias during declamping or that, in case of suboptimal heart preservation in the immediate post-transplant phase, a weakening of cardiac function may be observed.

Handling
Store in a refrigerator (2°C – 8°C). Do not freeze. Keep the bag in the outer aluminium-protected container to protect it from light.
The solution may develop a yellowish tint during storage. This does not affect the quality or efficacy of Celsior.
Although the packaging materials are produced under aseptic conditions, the outer surface of the Celsior bag is not sterile. Therefore, if Celsior is to be poured, the outer surface of the bag must be decontaminated.
Filtration of the solution prior to use is not required.
The outer aluminium-protected packaging contains substances capable of absorbing oxygen within a separate sachet, ensuring improved stability of the active substance reduced glutathione. The contents of the sachet must not be mixed with the solution.
The outer aluminium packaging and the oxygen-absorbing sachet must be removed before use.
After removal of the outer packaging, the inner container should be inspected for leaks by gently squeezing the bag. If a leak is detected, do not use the solution.
The Celsior bag has 3 openings. The tip of the cannula used to flush the organ must be inserted into the opening on the left side of the bag (by rotating it). The cannula must remain securely in place until the start of infusion.
The bag containing the solution should be placed inside a correctly sized sphygmomanometer cuff. The cuff should be inflated to apply sufficient pressure to squeeze out the fluid. Additionally, before infusion, the solution container should be suspended at a sufficient height to ensure a steady flow of solution.

Administration/Dosage

The organ is flushed via a cannula inserted into an artery, while maintaining sufficient pressure to ensure a steady flow of solution, in order to achieve adequate flushing. In liver transplantation, the biliary tree is generally flushed after explantation, before placing the organ into the storage and transport container.
The volume of flush solution depends on the organ.
Suggested minimum volumes:
Heart: adults: 1–2 litres
children: 30 ml/kg;
Liver: 6–8 litres;
Lung: 4–6 litres;
Kidney: 4–5 litres;
Pancreas: 4 litres;
Multi-organ: according to the individual organs involved.
Flushing should continue until the organ appears uniformly pale and the effluent is relatively clear.
After removal from cold storage (2–8°C), the cooled solution must be used immediately.

Paediatric patients
Although experience in children and adolescents is limited, there are no objections to the use of Celsior in this patient group.

Cold storage
The organ is stored at 5 ± 3°C in a sterile container of appropriate size.
The organ must be completely covered by the cooled solution. The organ storage container must be aseptically sealed.
The container should then be placed within at least one additional container. The latter should be filled with ice, ensuring that the ice does not enter the organ storage container, as direct contact between ice and the organ must be avoided. Ensure that the organ is stored aseptically within the container so that the interior of the organ storage container and its contents remain sterile.
Seal any additional containers securely.
Organ storage containers must be kept within a well-insulated transport container. The organ storage containers must be surrounded by ice.
Transport times should be minimized.