Corhum: detailed information

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

Contents of this leaflet:

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

1. What Corhum is and what it is used for

Corhum is a mixture of electrolytes and amino acids.
Corhum is used only during heart surgery and in organ harvesting for transplantation:

for induced and reversible cardiac arrest during open-heart surgical procedures (cardioplegia in cardiac surgery)
for organ protection during bloodless surgical procedures (heart, kidney, liver)
for organ transplant preservation: perfusion and cold storage (heart, kidney, liver, pancreas)

2. What you need to know before using Corhum

Corhum should only be used during surgical procedures.
Do not use Corhum

if you are allergic to the active substances or to any of the other ingredients of this medicine (listed in section 6). Warnings and precautions Consult your doctor before using Corhum. Inform your doctor if you are pregnant, as this will affect the use of the solution. For safety reasons, in the case of emergency cardiac surgery during pregnancy, the doctor will aspirate the perfusion solution from the right atrium and ventricle of the heart after completing the operation.

Corhum is not indicated for intravenous administration, but only for perfusion during cardiac arrest. Therefore, Corhum must not be used for systemic infusion.
Depending on the type of surgical procedure, the method used, the duration of the procedure, and the patient's weight, up to 3 litres of perfusion solution may enter the entire circulatory system. This may result in decreased blood levels of calcium and sodium. Your doctor will therefore carry out appropriate laboratory tests.
Children and adolescents
There is only limited data available on the use of Corhum in children and adolescents.
Other medicines and Corhum
Inform your doctor if you are taking or using, have recently taken or used, or might take or use any other medicines.
No interactions are known with the following medicines, which are mainly used during, but often also before and after surgery:

certain medicines used to treat heart failure (cardiac glycosides)
draining agents (diuretics)
medicines used to treat symptoms of angina pectoris (e.g. chest pain or tightness)
medicines used in conditions involving inadequate oxygen supply to the heart muscle (such as nitrates, beta-blockers, or calcium antagonists)
antihypertensive medicines (e.g. beta-blockers or calcium channel blockers).

Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, planning a pregnancy, or are breastfeeding, consult your doctor before using this medicine.
Driving and using machines
Corhum does not affect the ability to drive vehicles or operate machinery.
Corhum contains sodium and potassium
Corhum contains 345 mg of sodium (the main component of table salt) per 1000 ml.
This corresponds to 17% of the maximum recommended daily dietary intake of sodium for an adult.
Corhum contains 352 mg of potassium per 1000 ml. This should be taken into consideration in patients with reduced kidney function or in patients following a low-potassium diet.

3. How to use Corhum

The treatment regimen and dose must be determined by a specialist. Corhum must be administered only by a healthcare professional, i.e. a doctor or nurse. For dosage recommendations, refer to the detailed information for healthcare professionals at the end of this leaflet.

If more Corhum has been used than prescribed
Absorption of large amounts of Corhum into the circulation may lead to volume overload and electrolyte imbalances (abnormally low levels of calcium or sodium in the blood, or abnormally high levels of magnesium and potassium in the blood). In such cases, the doctor will perform periodic blood tests.
Note for the physician: further information on overdose is provided at the end of this leaflet.

If you have any doubts about how to use this medicine, consult your doctor or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Side effects with frequency not known (cannot be estimated from the available data):
The use of Corhum may lead to a temporary reduction in blood pressure during surgery.

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 through the national reporting system at the following website:
https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Corhum

Store in the refrigerator (2°C – 8°C) and keep the bag in the outer packaging to protect the medicine from light.
Do not freeze. After opening, use immediately.
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging after “Exp”. The expiry date refers to the last day of that month.
Unused medicine and waste material arising from this medicine must be disposed of in accordance with local regulations. These measures will help protect the environment.

6. Package contents and other information

What Corhum contains
The active substances are:
1000 ml of solution contain
0.8766 g Sodium chloride 15.0 mmol
0.6710 g Potassium chloride 9.0 mmol
0.8132 g Magnesium chloride hexahydrate 4.0 mmol
3.7733 g Histidine hydrochloride monohydrate 18.0 mmol
27.9289 g Histidine 180.0 mmol
0.4085 g Tryptophan 2.0 mmol
5.4651 g Mannitol 30.0 mmol
0.0022 g Calcium chloride dihydrate 0.015 mmol
0.1461 g 2-Oxoglutaric acid 1.0 mmol
The excipients are water for injections and potassium hydroxide (to adjust pH),
nitrogen.

Description of the appearance of Corhum and package contents
Use only if the solution is clear, colourless to slightly straw-yellow, in undamaged containers.
For single use only. Any unused residues must be discarded.
Corhum solution for cardioplegia is available in 1000 ml and 2000 ml bags (block copolymer polyolefin/styrene) with two tubes (block copolymer polyolefin/styrene) closed with a perforable stopper made of polyisoprene with silicated filler and polycarbonate, and an injection port made of chlorobutyl rubber. The bags are packed inside an overpouch made of polypropylene to ensure external sterility of the primary bag.

Pack sizes:
Carton box containing 10 bags of 1000 ml.
Carton box containing 5 bags of 2000 ml.
Not all pack sizes may be marketed.

Marketing Authorization Holder:
S.A.L.F. SpA Laboratorio Farmacologico
Via G. Marconi, 2
24069 Cenate Sotto (Bergamo)
Italy

Manufacturer:
S.A.L.F. SpA Laboratorio Farmacologico
Via G. Mazzini 9
24069 Cenate Sotto (Bergamo)
Italy

This medicinal product is authorized in the European Economic Area countries and in the United Kingdom (Northern Ireland) under the following names:
Austria Corhum Kardioplege Lösung / Organkonservierungslösung
Denmark Corhum
Finland Corhum liuos sydämenpysäytystä varten / elintensäilytysneste
Italy Corhum solution for cardioplegia / organ preservation
Norway Corhum oppløsning til kardioplegi / organoppbevaring
United Kingdom (Northern Ireland) Corhum solution for cardioplegia / organ preservation
Spain Corhum solución para cardioplejia / conservación de órganos
Sweden Corhum, lösning för kardioplegi / organförvaring

The following information is intended exclusively for healthcare professionals:

Complete inactivation renders the myocardium susceptible to distension. It is therefore essential to ensure adequate ventricular drainage. Do not exceed the recommended perfusion volumes and pressures. Particular caution is advised for hearts of children and infants.

Overdose
The passage of large volumes of Corhum into the systemic circulation may lead to volume overload and electrolyte imbalances (hypocalcemia, hyponatremia, hypermagnesemia, hyperkalemia). After systemic administration, regular monitoring of serum electrolytes is recommended.

Dosage and method of administration

Adults

A. Cardioplegia
Perfusion volume:

Open-heart procedures: Solution temperature 6 °C – 10 °C for open-heart procedures
Perfusion rate is 1 ml/minute/gram of heart weight. Normal heart weight corresponds to approximately 0.5% of an adult's body weight, resulting in a total Corhum volume between 1.5 and 2 liters.

Perfusion pressure (= pressure in the aortic root):
Initially, 110–140 cm of hydrostatic pressure (equivalent to 80–110 mmHg) is used in adults. The surgeon must ensure proper closure of the aortic valve. After cardiac arrest, reduce the pressure by half to 50–70 cm of hydrostatic pressure (equivalent to 40–50 mmHg). In cases of severe coronary stenosis, use a higher pressure (approximately 50 mmHg).

Perfusion time:
With this dosage and pressure regimen, a perfusion time of 6–8 minutes is required to achieve homogeneous myocardial equilibration and must not be shortened under any circumstances.

Perfusion technique:
After aortic clamping and simultaneous "drainage" of the left ventricle, administer the solution antegrade. Cardioplegic perfusion can be performed using a roller pump with constant volume or by gravity (after cardiac arrest, the solution bag should be maintained at 40–50 cm above heart level).

Guidelines for additional cardioplegic perfusions:
If additional cardioplegic perfusions are required, the perfusion time should be 1–2 minutes (equivalent to 200–400 ml); perfusion pressure should correspond to that used in the last minute of the initial cardioplegic coronary perfusion.

In most cases, moderate systemic hypothermia should be induced.

Normally, Corhum is administered via the aortic root. In cases of aortic insufficiency or surgery for thoracic aortic dissection, the solution should be administered via selective coronary perfusion into the coronary ostia.

Due to the limited amount of clinical data, a positive benefit-risk ratio for the use of Corhum in short surgical procedures (<90 minutes) has not yet been established.

Guidelines for retrograde perfusion into the coronary sinus:
Do not exceed an infusion pressure of 30 mmHg (normally about 250 ml/min) for retrograde infusion of the same duration as antegrade infusion (at least 6–8 minutes).

B. Heart transplantation
After cross-clamping of the ascending aorta, perfuse the heart for at least 6 minutes. This corresponds to a perfusion rate of 1 ml/minute per gram of heart weight, up to a total of 3.5 liters or more in adults.

Perfusion pressure (= pressure in the aortic root):
Initially, 110–140 cm of hydrostatic pressure (equivalent to 80–110 mmHg) is used in adults. The surgeon must ensure proper closure of the aortic valve. After cardiac arrest, reduce the pressure to 50–70 cm of hydrostatic pressure (equivalent to 40–50 mmHg). In cases of severe coronary stenosis, use a higher pressure (approximately 50 mmHg).

Perfusion time:
With this dosage and pressure regimen, a perfusion time of 6–8 minutes is required to achieve homogeneous myocardial equilibration and must not be shortened under any circumstances.

Perfusion technique:
After aortic clamping and simultaneous "drainage" of the left ventricle, administer the solution antegrade. Cardioplegic perfusion can be performed using a roller pump with constant volume or by gravity (after cardiac arrest, the solution bag should be maintained 40–50 cm above heart level).

If the heart perfused with Corhum is intended for transplantation, it must be stored and transported in cold Corhum solution at 2°C–4°C to maintain protection. This provides effective protective effects for at least five hours.

C. Kidney transplantation
The following general usage guidelines are recommended for the kidney:

Solution temperature: 5°C – 8°C

Perfusion volume:
Perfuse with 1.5 ml of Corhum per minute per gram of estimated kidney weight (normal adult kidney weight is approximately 150 grams). Including 500 ml of preservation solution, a total volume of approximately 2.5 liters of Corhum per organ is obtained.

Perfusion pressure (renal artery):
120–140 cm water column above kidney level, equivalent to approximately 90–110 mmHg at the tip of the perfusion catheter in the renal artery.

Perfusion time:
Using this dosage and pressure regimen, perfusion time is 8–10 minutes. This duration is necessary to ensure homogeneous equilibration of the kidney's extracellular space (including interstitial tissues and the renal tubular system) and must not be reduced under any circumstances.

Concomitant measures:
To achieve maximum benefit from Corhum’s protective effect on the kidney, it is important to ensure marked diuresis before starting perfusion (pharmacologically and/or through patient hydration).

Corhum is administered through the renal artery.

If the kidney perfused with Corhum is intended for transplantation, it must be stored and transported in cold Corhum solution at 2°C–4°C to maintain the protective effect. This provides effective protection for up to 48 hours.

D. Liver transplantation
The following general usage guidelines are recommended for the liver:

Solution temperature: 5°C – 8°C

Perfusion time:
With this dosage and pressure regimen, perfusion time is 8 minutes (10–15 minutes).

Perfusion volume:
If simultaneous protection of liver, pancreas, and kidney is intended in a so-called multi-organ donor, a perfusion volume of 150–200 ml of Corhum solution/kg body weight is required. With this "general protection," this corresponds to a perfusion volume of cold Corhum solution of 8–12 liters in patients weighing approximately 70–80 kg.

For surgical removal of the liver or part of the liver (e.g., in living donors) without other organs, the perfusion volume should be reduced accordingly.

Perfusion pressure:
100 cm water column above liver level.

Concomitant measures:
In organ donors, blood must be heparinized before the start of perfusion.

Additionally, for transplantation:
Bile ducts must be abundantly irrigated with at least 100 ml of cold Corhum solution, either in situ or ex situ—usually with the aid of a small-caliber catheter.

The surgically removed liver is packaged or shipped for transplantation immersed in cold Corhum solution. The organ must be completely covered with cold Corhum solution. A cold ischemia time of <10 hours is recommended.

E. Pancreas
The volume and duration of perfusion used for the liver must be adapted for the pancreas, a much smaller organ. Optimal perfusion depends on careful cooling and blood removal from the organ, achieved using approximately 3–4 liters of Corhum. Avoid excessive treatment and further irrigation of the organ.

Previous research data suggest caution should be exercised to avoid over-irrigation of pancreatic allografts with any preservation solution, as this may induce edema and allograft pancreatitis; furthermore, there appears to be a clear benefit in keeping cold ischemia time as short as possible. A cold ischemia time of <10 hours is recommended.

With larger irrigation volumes (>5 liters) and longer ischemia times (>12 hours), there may be a risk of allograft pancreatitis.

Pediatric population
Limited data are available regarding use in children and adolescents.

Heart

Perfusion pressure: in neonates and infants, initially 110–120 cm water column above heart level (equivalent to 80–90 mmHg); after cardiac arrest, reduce pressure to 40–50 cm water column (equivalent to 30–40 mmHg). In patients with severe coronary sclerosis, maintain higher pressure for a longer period. Open the right atrium and completely aspirate the cardioplegic solution from the bypass circuit to avoid hemodilution.
Perfusion volume depends on the child's age: 50 ml/kg (first month of life), 30 ml/kg (2nd month–1st year), 20 ml/kg (>1st year), with a perfusion time of 4–6 minutes in all cases.

Incompatibilities
In the absence of compatibility studies, Corhum must not be mixed with other medicinal products.