Kybernin p
Poland
Table of Contents
Package leaflet: Information for the patient
KYBERNIN P
500 IU
Powder and solvent for solution for infusion, 50 IU/mL
Human antithrombin III
Please read this leaflet carefully before using this medicine, because it contains important information for the patient.
- Keep this leaflet. You may need to read it again.
- If you have any further questions, please ask your doctor or pharmacist.
- This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm them even if their symptoms are the same.
- If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.
Leaflet contents:
- What KYBERNIN P is and what it is used for
- Important information before using KYBERNIN P
- How to use KYBERNIN P
- Possible side effects
- How to store KYBERNIN P
- Contents of the pack and other information
1. What KYBERNIN P is and what it is used for
KYBERNIN P is an anticoagulant medicine containing antithrombin derived from human plasma. Antithrombin is a natural component of human plasma and an important inhibitor of blood coagulation.
KYBERNIN P is used in the treatment of congenital antithrombin III deficiency:
a) for venous thrombosis and thromboembolic disease in clinical risk situations (especially during surgical procedures or the peripartum period), in combination with heparin, when heparin is indicated.
b) for prevention of deep vein thrombosis and thromboembolic disease, in combination with heparin, according to indications.
KYBERNIN P is also used in the treatment of 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 to any of the other components of this medicine (listed in section 6).
Warnings and precautions
Before starting treatment with KYBERNIN P, discuss this with your doctor or pharmacist.
As with any intravenous medicinal product, allergic-type hypersensitivity reactions may occur. The patient must be under close monitoring and careful observation for any symptoms during the infusion. The treating physician or medical staff should inform the patient about early signs of hypersensitivity reactions, including urticaria, generalized rash, chest tightness, wheezing, drop in blood pressure, and anaphylaxis. If such symptoms occur after administration of the medicine, the patient should contact their doctor immediately.
In case of shock, the treating physician or medical personnel will initiate standard treatment.
Safety regarding the possibility of viral transmission
For medicinal products prepared from human blood or plasma, measures are taken to prevent infection of patients. These include:
- careful selection of blood and plasma donors to ensure that donors at risk of transmitting infections are excluded,
- testing of each donation and plasma pool for the presence of viruses/infections,
- inclusion in the manufacturing process of procedures capable of inactivating or removing viruses.
Despite these measures, it is not possible to completely exclude the risk of transmitting infection when administering medicines derived from human blood or plasma. This also applies to currently unknown or newly emerging viruses and other types of infections.
The procedures used are considered effective against enveloped viruses such as human immunodeficiency virus (HIV, the virus causing AIDS), hepatitis B virus, hepatitis C virus (liver inflammation), as well as against non-enveloped viruses such as hepatitis A virus (liver inflammation) and parvovirus B19.
Parvovirus B19 infection may be dangerous for pregnant women (due to the risk of fetal infection) and for patients with immunodeficiencies or certain types of anemia (e.g. sickle cell anemia or hemolytic anemia).
If the patient regularly or repeatedly receives products derived from human plasma (e.g. factor IX), the doctor may recommend vaccination against hepatitis A and B.
The treating physician should consider appropriate vaccination (against hepatitis A and B) for patients with congenital deficiency who regularly receive antithrombin concentrates derived from plasma.
It is strongly recommended that, with every administration of KYBERNIN P, the product name and batch number be recorded to allow traceability to the patient.
Clinical and biological monitoring when using antithrombin together with heparin:
- to determine heparin dosage and avoid excessive anticoagulant effect, regular control tests of anticoagulant activity (APTT, and if indicated, anti-FXa activity) should be performed frequently, especially during the first minutes/hours after starting antithrombin therapy.
- daily measurement of antithrombin levels should be performed to determine individual dosing, due to the risk of decreased antithrombin levels resulting from prolonged treatment with unfractionated heparin.
Children and adolescents
Based on clinical studies, the use of antithrombin for the treatment of infant respiratory distress syndrome (IRDS) in premature infants cannot be recommended.
KYBERNIN P and other medicines
Inform your doctor or pharmacist about all medicines currently used, recently used, or planned for use.
Heparin: concomitant use of antithrombin during therapeutic-dose heparin therapy increases the risk of bleeding. Heparin significantly enhances the effect of antithrombin. The half-life of antithrombin may be considerably reduced during concomitant heparin therapy due to increased consumption of antithrombin. Therefore, concomitant administration of heparin and antithrombin to patients with increased bleeding risk must be clinically and biologically monitored.
The use of hydroxyethyl starch (HES) as an infusion diluent is not recommended, as it has been observed to reduce antithrombin activity.
The medicinal product must not be mixed with other medicinal products in the same syringe or infusion set, except as specified in section 3. Dopamine, dobutamine, and furosemide should not be administered through the same intravenous access.
Pregnancy, breastfeeding, and fertility
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a child, she should consult her doctor or pharmacist before using this medicine.
There are only limited data available on the safety of products containing human antithrombin in pregnant women.
The safety of KYBERNIN P use during pregnancy has not been confirmed in controlled clinical trials. Animal studies are insufficient to assess safety with respect to reproduction, embryonic and fetal development, course of pregnancy, and pre- and postnatal development.
There are 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 clearly indicated, taking into account that in this patient group, pregnancy increases the risk of thromboembolic events.
Driving and using machines
KYBERNIN P has no effect or a negligible effect on the ability to drive and operate machinery.
KYBERNIN P contains sodium
KYBERNIN P contains up to 44.76 mg of sodium per vial. This should be taken into consideration in patients on a controlled low-sodium diet.
3. How to use KYBERNIN P
This medicine should always be used as directed by the physician. In case of doubt, consult your doctor or pharmacist.
Recommended dose
The appropriate dose will be determined by the physician.
In congenital deficiency, dosing should be individually adjusted for each patient, taking into account family history of thromboembolic events, current clinical risk factors, and laboratory evaluation.
Dosing and duration of replacement therapy in acquired deficiency depend on plasma antithrombin levels, signs of increased consumption, underlying disease, and the patient's clinical condition. The dose and frequency of administration should always be individually determined based on clinical efficacy and laboratory test results.
The amount of administered antithrombin is expressed in international units (IU), referring 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 for antithrombin content in plasma).
One international unit (IU) of antithrombin activity corresponds to the amount of antithrombin contained in 1 ml of normal human plasma. The conversion of the required antithrombin dose is based on the empirical observation that 1 international unit (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 number of units = body weight [kg] × (100 – current antithrombin activity [%]) × 2/3
The initial target antithrombin activity depends on the clinical condition. Once the indication for antithrombin replacement therapy has been established, the dose should be sufficient to achieve the target antithrombin activity and maintain a level ensuring efficacy. Dosing should be determined and monitored based on laboratory measurements of antithrombin activity, which should be performed at least twice daily, and once daily when the patient's condition stabilizes, preferably just before the next infusion. Dose adjustments should consider both signs of increased antithrombin consumption, as indicated by laboratory results, and the clinical course.
Antithrombin activity should be maintained above 80% throughout the entire treatment period, unless specific clinical data indicate that another effective activity level should be applied.
In congenital deficiency, the initial dose is usually 30–50 IU/kg.
Subsequently, the dose, frequency of administration, and duration of therapy should be adjusted according to biological data and clinical status.
Children and adolescents
40–60 IU of antithrombin per kilogram of body weight per day, depending on the patient's coagulation status. The dose may be increased in individual cases if clinically required. In such cases, antithrombin activity must be monitored more frequently and should not exceed 120%.
Use of a higher than recommended dose of KYBERNIN P
No symptoms related to antithrombin overdose have been reported.
Method of administration
The powder must be completely reconstituted under aseptic conditions using the solvent provided. The resulting solution should be colorless to slightly opalescent.
For infusion, 5% human albumin solution is an appropriate diluent. To prepare dilutions of 1:5, the following solutions may also be used: sodium lactate Ringer's solution, physiological saline solution, 5% glucose solution, or polygeline.
Do not use solutions that are cloudy or contain sediment.
The solution should be administered slowly by intravenous injection or slow infusion, at a maximum rate of 4 ml/min.
4. Possible adverse reactions
Like any medicine, this medicinal product may cause adverse reactions, although not in everyone.
Hypersensitivity or allergic reactions (including angioedema, burning and stinging at the infusion site, chills, sudden facial flushing, generalized urticaria, headache, urticaria, hypotension, drowsiness, nausea, restlessness, tachycardia, chest tightness, tingling, vomiting, wheezing) have been observed rarely and, in some cases, may develop into severe anaphylaxis (including anaphylactic shock).
Fever has occurred in rare cases.
Information regarding safety in terms of the possibility of viral transmission is included in section 2.
Reporting suspected adverse reactions
If any adverse symptoms occur, including any adverse effects not listed in this leaflet, inform your doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products:
Al. Jerozolimskie 181C
02-222 Warsaw
Tel.: +48 22 49 21 301
Fax: +48 22 49 21 309
e-mail: [email protected]
Adverse reactions may also be reported to the marketing authorization holder.
Reporting of suspected adverse reactions helps to increase the safety information available for this medicinal product.
5. How to store KYBERNIN P
The medicine should be stored in a place inaccessible and out of sight 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 stated month.
Store below 25°C. Do not freeze.
After reconstitution, physicochemical stability is maintained for 8 hours at a temperature below 25°C.
From a microbiological point of view, and due to the fact that KYBERNIN P does not contain preservatives,
the product should be used immediately after reconstitution. If not administered immediately, storage should not exceed 8 hours at a temperature below 25°C.
After opening the container, its contents should be used immediately.
Do not use this medicine if the solution appears cloudy or contains particles.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. 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 for pH adjustment), 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 colourless glass (type II), closed with a bromobutyl rubber stopper, plastic cap, and aluminium seal.
One pack (500 IU) contains:
1 vial with powder
1 vial with 10 ml of water for injections
1 double-ended needle
Marketing Authorisation Holder and Manufacturer
CSL Behring GmbH
Emil-von-Behring-Str. 76
D-35041 Marburg
Germany
For further information, please contact the local representative of the Marketing Authorisation Holder:
CSL Behring sp. z o.o.
Ul. Branickiego 17
02-972 Warszawa
Poland
Tel: 22 213 22 65