Kibernin P

PATIENT INFORMATION LEAFLET

Enclosed leaflet: patient information

KYBERNIN P

500 IU
Powder and solvent for solution for infusion, 50 IU/ml.
Human antithrombin III
Read the leaflet carefully before using the medicine, as it contains important information for the patient.
This leaflet provides important information for the patient.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Table of contents of the leaflet:

• 1. What is KYBERNIN P and what is it used for
• 2. Important information before using KYBERNIN P
• 3. How to use KYBERNIN P
• 4. Possible side effects
• 5. How to store KYBERNIN P
• 6. Contents of the pack and other information

1. What is KYBERNIN P and what is it used for

KYBERNIN P is an anticoagulant medicine that contains antithrombin from human plasma. Antithrombin is a normal component of human plasma and an important inhibitor of blood coagulation.
KYBERNIN P is used to treat hereditary antithrombin III deficiency:
a) deep vein thrombosis and thromboembolic disease in clinical risk situations (especially during surgical procedures or during the peripartum period) in combination with heparin, if there are indications for its administration.
b) the development of deep vein thrombosis and thromboembolic disease in combination with heparin, according to the indications.
KYBERNIN P is used to treat acquired antithrombin III deficiency.

2. Important information before using KYBERNIN P

When not to use KYBERNIN P:

• if the patient is allergic to antithrombin III or any other component of this medicine (listed in section 6).

Warnings and precautions

Before starting treatment with KYBERNIN P, discuss it with your doctor or pharmacist.
As with any intravenous preparation, allergic reactions are possible. The patient will be under close monitoring and careful observation of all symptoms during the infusion. The treating doctor or medical staff should inform the patient about the early symptoms of an allergic reaction, which include hives, generalized hives, chest tightness, wheezing, decreased blood pressure, and anaphylaxis. If such symptoms occur after administration of the medicine, the patient should contact their doctor.
In case of anaphylaxis, the treating doctor or medical staff will apply standard treatment.
Safety of use in terms of the possibility of virus transmission
For medicines produced from human blood or plasma, precautions are taken to prevent patient infection. These include:

• careful selection of blood and plasma donors to ensure that donors at risk of transmitting infections are excluded,
• testing each donation and plasma pool for the presence of viruses/infections,
• including a procedure in the blood or plasma processing process that can inactivate or remove viruses.

Despite their use, when administering medicines prepared from human blood or plasma, it is not possible to completely exclude the possibility of transmitting an infection. This also applies to unknown or newly discovered viruses and other types of infections.
The procedures used are considered effective against enveloped viruses, such as human immunodeficiency virus (HIV, the virus that causes AIDS), hepatitis B virus, and hepatitis C virus (inflammatory liver disease), as well as against non-enveloped viruses such as hepatitis A virus (inflammatory liver disease) and parvovirus B19.
Parvovirus B19 infection can be dangerous for pregnant women (due to the risk of infecting the fetus) and for patients with immune deficiencies or certain types of anemia (e.g., sickle cell anemia or hemolytic anemia).
If the patient regularly/takes products obtained from human plasma (e.g., factor IX), the doctor may recommend vaccination against viral hepatitis A and B.
The treating doctor should consider appropriate vaccination (against viral hepatitis A and B) in patients with hereditary deficiency who regularly take antithrombin concentrates from plasma.
It is strongly recommended that when administering KYBERNIN P, the product name and batch number be recorded, in order to enable it to be linked to the patient.
Clinical and biological monitoring when using antithrombin with heparin:

• to determine the heparin dosage and avoid excessive anticoagulant effect, regular checks of the anticoagulant effect (APPT, and if indicated, anti-FXa activity) should be performed at short intervals, especially in the first minutes/hours after starting antithrombin treatment.
• daily measurement of antithrombin levels should be performed to determine the individual dose, due to the risk of decreased antithrombin levels due to long-term treatment with unfractionated heparin.

Children and adolescents

Based on clinical studies, the use of antithrombin to treat neonatal respiratory distress syndrome (IRDS) in premature infants cannot be recommended.

KYBERNIN P and other medicines

Tell your doctor or pharmacist about all medicines you are currently taking or have recently taken, as well as any medicines you plan to take.
Heparin: the use of antithrombin during heparin administration in therapeutic doses increases the risk of bleeding. Heparin significantly increases the effects of antithrombin. The half-life of antithrombin may be significantly reduced during concurrent heparin therapy, due to increased antithrombin consumption. Therefore, concurrent administration of heparin and antithrombin to patients with increased risk of bleeding must be clinically and biologically monitored.
The use of hydroxyethyl starch (HES) is not recommended as a diluent (for infusion), as it has been observed to decrease antithrombin activity.
Do not mix the medicinal product with other medicinal products in a syringe or infusion set, except for those mentioned in section 3. Dopamine, dobutamine, and furosemide should not be administered through the same intravenous access.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or plan to have a child, consult your doctor or pharmacist before using this medicine.
There is only limited data on the safety of using products containing human antithrombin in pregnant women.
The safety of using KYBERNIN P in pregnant women has not been confirmed in controlled clinical trials. Animal studies are insufficient to assess safety in relation to reproduction, embryonic and fetal development, pregnancy, and pre- and post-natal development.
There is no data on treatment during pregnancy and lactation. Therefore, KYBERNIN P should be administered to women with antithrombin deficiency during pregnancy and lactation only if it is clearly indicated, taking into account that pregnancy increases the risk of thromboembolic events in this patient group.

Driving and using machines

KYBERNIN P has no influence or negligible influence on the ability to drive and use machines.

KYBERNIN P contains sodium

KYBERNIN P contains up to 44.76 mg of sodium per vial. This should be taken into account in patients on a controlled low-sodium diet.

3. How to use KYBERNIN P

This medicine should always be used as directed by your doctor. If you are unsure, consult your doctor or pharmacist.

Recommended dose

The doctor will decide on the use of the appropriate dose.
For hereditary deficiency, dosing should be individualized for each patient, taking into account the family history of thromboembolic events, current clinical risk factors, and laboratory assessment.
Dosing and duration of substitution therapy for acquired deficiency depend on antithrombin levels in plasma, signs of increased consumption, underlying disease, and the severity of the patient's clinical condition. The dose and frequency of administration should always be determined individually based on clinical efficacy and laboratory results.
The amount of antithrombin administered is expressed in international units (IU), which refer to the current WHO standards for antithrombin. Antithrombin activity in plasma is expressed as a percentage (relative to normal human plasma) or in international units (relative to international standards of antithrombin content in plasma).
One international unit (IU) of antithrombin activity corresponds to the amount of antithrombin contained in one ml of normal human plasma. The calculation of the required dose of antithrombin is based on the empirical finding that 1 IU of antithrombin per kg of body weight increases antithrombin activity by approximately 1.5%.
The initial dose is calculated using the following formula:
Required units = body weight [kg] x (100 - current antithrombin activity [%]) x 2/3)
The target antithrombin activity depends on the clinical condition. When the indication for substitution therapy with antithrombin is established, dosing should be sufficient to achieve the target antithrombin activity and maintain a level that ensures efficacy. Dosing should be determined and monitored based on laboratory measurements of antithrombin activity, which should be performed at least twice a day, and when the patient's condition stabilizes, once a day, preferably before the next infusion. Dose adjustment should take into account both signs of increased antithrombin consumption, according to laboratory results, and the clinical course.
Antithrombin activity should be maintained above 80% throughout the treatment period, unless specific clinical data indicate that a different effective level of activity should be used.
For hereditary deficiency, the initial dose is usually 30-50 IU/kg.
Subsequently, dosing and frequency of administration, as well as the duration of therapy, should be adjusted based on biological data and clinical condition.

Children and adolescents

40-60 IU of antithrombin per kilogram of body weight per day, depending on the patient's coagulation system condition. The dose can be increased in individual cases if the clinical situation requires it. Then, antithrombin activity must be monitored more frequently and should not exceed 120%.

Use of a higher than recommended dose of KYBERNIN P

No symptoms associated with antithrombin overdose have been reported.

Method of administration

The powder should be completely reconstituted under aseptic conditions in the enclosed solvent. The resulting solution should be colorless to slightly opalescent.
For infusion, a suitable diluent is a 5% solution of human albumin. To prepare a 1:5 dilution, the following solutions can also be used: Ringer's solution with lactate, physiological saline solution, 5% glucose solution, or polygeline.
Do not use solutions that are cloudy or contain sediment.
The solution should be slowly injected or administered in a slow intravenous infusion at a maximum rate of 4 ml/min.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Allergic reactions or hypersensitivity reactions (which may include angioedema, flushing, and injection site reactions such as redness, itching, and hives, chills, sudden flushing, generalized hives, low blood pressure, drowsiness, nausea, anxiety, tachycardia, chest tightness, paresthesia, vomiting, wheezing) have been observed rarely, and in some cases, may develop into severe anaphylaxis (with anaphylactic shock).
Fever has occurred in rare cases.
Information on the safety of use in terms of the possibility of virus transmission is contained in section 2.
Reporting suspected adverse reactions
If you experience any side effects, including those not listed in this leaflet, tell your doctor or pharmacist. Adverse reactions can be reported directly to the Department of Drug Safety, Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products:
Al. Jerozolimskie 181C
02-222 Warsaw
Phone: +48 22 49 21 301
Fax: +48 22 49 21 309
e-mail: [email protected]
Adverse reactions can also be reported to the marketing authorization holder.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store KYBERNIN P

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the label and carton after EXP.
The expiry date refers to the last day of the month stated.
Store in a temperature below 25°C. Do not freeze.
After reconstitution, the physical and chemical stability is maintained for 8 hours at a temperature below 25°C. From a microbiological point of view and considering that KYBERNIN P does not contain preservatives, the reconstituted product should be used immediately. If not used immediately, storage should not exceed 8 hours at a temperature below 25°C.
After opening the package, its contents should be used immediately.
Do not use this medicine if you notice that the solution is cloudy or contains sediment.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines that are no longer needed. This will help protect the environment.

6. Contents of the pack and other information

What KYBERNIN P contains

The active substance is human antithrombin III
The other ingredients are: glycine, sodium chloride, sodium citrate, sodium hydroxide or hydrochloric acid (in small amounts to adjust the pH), water for injections (for reconstitution).

What KYBERNIN P looks like and contents of the pack

Kybernin P is available as a powder and solvent for solution for infusion.
The vial is made of colorless glass (type II) closed with a bromobutyl rubber stopper, a plastic cap, and an aluminum cap.
One pack (500 IU) contains:
1 vial with powder
1 vial with water for injections of 10 ml
1 double-ended needle

Marketing authorization holder and manufacturer

CSL Behring GmbH
Emil-von-Behring-Str. 76
D-35041 Marburg
Germany
To obtain more detailed information, contact the representative of the marketing authorization holder:
CSL Behring sp. z o.o.
Ul. Branickiego 17
02-972 Warsaw
Phone: 22 213 22 65

Date of last revision of the leaflet: