Kybernin P 500 IU, powder and solvent for solution for injection or infusion

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Kybernin P 500 IU powder and solvent for solution for injection and for infusion

Human Antithrombin III

Read the entire leaflet carefully before you start using this medicine, because it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only, and you should not give it to other people, even if they have the same symptoms as you, because it could harm them.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are adverse effects not listed in this leaflet. See section 4.

Contents of the leaflet

1. What Kybernin P is and what it is used for
2. What you need to know 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 Kybernin P is and what it is used for

Kybernin P is a powder and solvent for injectable solution and for perfusion.

This medicinal product belongs to a group of medicines called antithrombotic agents.

Kybernin P is used if you have congenital antithrombin deficiency, to prevent the formation and development of blood clots in the blood vessels of your legs (deep vein thrombosis) or in other vessels of your body (thromboembolism) during surgery or in the peripartum period, and in combination with heparin if indicated.

Kybernin P is also used if you have acquired antithrombin deficiency.

2. What you need to know before starting to use Kybernin P

Do not use Kybernin P:

If you are allergic to the active substance or to any of the other components of this medicine (listed in section 6).

Warnings and precautions

As with any protein product for intravenous administration, allergic-type hypersensitivity reactions may occur. Close monitoring and careful observation of patients are required to detect any symptoms during the infusion period. Patients should be informed about the early signs of hypersensitivity reactions, which may include skin rashes that can progress to generalized urticaria, chest tightness, difficulty breathing, hypotension, and anaphylaxis. If these symptoms occur after administration, contact your doctor.

In the event of shock, current guidelines for shock treatment should be followed.

Viral safety

When administering medicinal products derived from human blood or plasma, certain measures must be taken to prevent transmission of infections to patients. These measures include:

• Careful selection of donors to exclude those at risk of carrying infectious diseases,
• Testing for specific markers of infection in individual donations and plasma pools,
• Inclusion of steps in the manufacturing process to eliminate/inactivate viruses.

Despite these measures, the possibility of transmitting infectious agents cannot be completely ruled out when administering medicines derived from human blood or plasma. This also applies to emerging or unknown viruses and other types of infections.

The measures taken are considered effective against enveloped viruses such as human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), and against non-enveloped viruses such as hepatitis A virus (HAV) and parvovirus B19.

Your doctor may recommend that you consider vaccination against hepatitis A and B if you regularly receive products containing antithrombin derived from human plasma.

It is highly recommended that each time Kybernin P is administered to a patient, the name of the medicine and the batch number used should be recorded, in order to maintain traceability between the patient and the product batch.

Clinical and biological monitoring when antithrombin and heparin are administered together:

• To adjust the heparin dose and avoid excessive anticoagulation, regular monitoring of the degree of anticoagulation (aPTT, and when appropriate, anti-FXa activity) should be performed at short intervals, especially during the first minutes/hours after starting antithrombin administration.
• Daily determination of antithrombin levels to adjust the individual dose, due to the risk of decreased antithrombin levels as a result of prolonged treatment with unfractionated heparin.

Use of Kybernin P with other medicines

Heparin: Replacement of antithrombin during administration of therapeutic doses of heparin increases the risk of bleeding. The effect of antithrombin is greatly enhanced by heparin. The half-life of antithrombin may be considerably reduced by concomitant heparin treatment due to accelerated clearance of antithrombin. Therefore, simultaneous administration of heparin and antithrombin in a patient with a high risk of bleeding should be clinically and biologically monitored.

Inform your doctor or pharmacist if you are using, have recently used, or might need to use any other medicines.

Pregnancy, lactation and fertility

Experience regarding the safety of human antithrombin products for use during human pregnancy is limited.

The safety of using Kybernin P during human pregnancy has not been established in controlled clinical trials. Animal studies are insufficient to assess safety with respect to reproduction, embryonic or fetal development, course of gestation, and peri- and postnatal development.

There are no negative experiences reported regarding treatment during pregnancy and lactation.

Therefore, Kybernin P should be administered to pregnant or breastfeeding women with antithrombin deficiency only if clearly indicated, taking into account that pregnancy itself increases the risk of thromboembolic episodes in these patients.

If you are pregnant, breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medicinal product. Your doctor will weigh the potential risk to the fetus and inform you whether treatment with this medicine is appropriate. Your doctor will recommend this treatment only if it is clearly indicated.

Driving and Use of Machinery

There is no indication that Kybernin P may affect the ability to drive vehicles or operate machinery.

Kybernin P 500 UI contains sodium

Patients on sodium-restricted diets should be aware that Kybernin P 500 UI contains up to 44.76 mg (1.947 mmol) of sodium per 500 UI.

3. How to use Kybernin P

Kybernin P is a hospital-use medicine, so it will be administered to you in a
hospital by the appropriate healthcare staff.

Kybernin P is administered by first preparing a solution, which is then slowly injected or infused intravenously (maximum 4 ml/min).

Follow exactly the administration instructions for this medicine as indicated by your doctor or pharmacist. If in doubt, consult your doctor or pharmacist again.

Your doctor will determine how frequently and at what intervals Kybernin P should be administered.

Your doctor will inform you of the duration of your treatment with Kybernin P.

If you use more Kybernin P than you should:

Symptoms of overdose with antithrombin have not been reported.
In case of overdose or accidental administration, contact the Toxicology Information Service. Telephone 91 562 04 20.

If you forget to use Kybernin P:

• Consult your doctor or pharmacist immediately.
• Do not administer a double dose to make up for missed doses.

4. Possible adverse effects

Like all medicines, this medicine may cause adverse effects, although not everyone will experience them.

The following adverse reactions are based on post-marketing experience. When data are available, the following standard frequency categories have been used:

Very common >1/10

Common >1/100 to <1/10

Uncommon ≥1/1,000 to <1/100

Rare ≥1/10,000 to <1/1,000

Very rare <1/10,000 (including individual cases reported)

For information on viral safety, see “Warnings and precautions” in section 2 of this leaflet.

Reporting of adverse reactions

If you experience any type of adverse reaction, consult your doctor or pharmacist, even if it is an adverse reaction not listed in this leaflet. You may also report them directly via the Spanish Pharmacovigilance System for Human Medicinal Products: https://www.notificaram.es. By reporting adverse reactions, you can help provide more information on the safety of this medicine.

5. Storage of Kybernin P

Keep this medicine out of the sight and reach of children.

Do not store above 25 °C. Do not freeze.

Do not use this medicine after the expiry date stated on the container after EXP. The expiry date refers to the last day of the month indicated.

Do not use solutions that are cloudy or contain residues (deposits/particles).

After reconstitution, physico-chemical stability has been demonstrated for up to 8 hours at room temperature (maximum 25 °C). From a microbiological standpoint, and since Kybernin P does not contain preservatives, the reconstituted solution should be used immediately. If this is not possible, do not store for longer than 8 hours at room temperature (maximum 25 °C).

Any unused medicinal product or waste material must be disposed of in accordance with local regulations.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and containers you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of Kybernin P 500 IU

• The active substance is antithrombin III. Each lyophilized vial contains 500 IU of antithrombin III. The reconstituted solution contains approximately 50 IU of antithrombin III/mL of antithrombin derived from human plasma when reconstituted with 10 mL of water for injections.

The potency (IU) is determined using the Chromogenic Substrate Method according to the European Pharmacopoeia. The specific activity of Kybernin P is approximately 5.3 IU/mg of protein.

• The other components are: glycine, sodium chloride, sodium citrate, hydrochloric acid or sodium hydroxide (to adjust pH), and water for injections.

See section 2 for important information regarding some of the excipients.

Nature of the product and contents of the container

Powder and solvent for solution for injection and infusion.

The marketing pack contains a molded glass type II (according to Ph. Eur.), colorless vial sealed with a rubber stopper, plastic disc, and aluminum cap containing the lyophilized powder, one vial with 10 mL of water for injections (solvent for solution preparation), and a transfer device.

Presentations:

Individual pack of Kybernin P 500 IU:

1 vial of lyophilized powder
1 vial with 10 mL of water for injections
1 transfer device

Clinical pack of Kybernin P 500 IU:

10 vials of lyophilized powder
10 vials with 10 mL of water for injections
10 transfer devices

Only certain pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

CSL Behring, S.A.
C/ Tarragona 157, 18th floor
08014 Barcelona - Spain

Manufacturer

CSL Behring GmbH
Emil-von-Behring-Str. 76
35041 Marburg - Germany

Date of the most recent review of this leaflet: November 2020

Detailed and up-to-date information on this medicine is available on the website of the Spanish Agency of Medicines and Health Products (AEMPS) http://www.aemps.gob.es

This information is intended for healthcare professionals only:

Dosage

In congenital deficiency, the dose should be individualized for each patient, taking into account family history regarding thromboembolic episodes, the patient's clinical risk factors, and laboratory tests.

The dosage and duration of replacement therapy in acquired deficiency depend on plasma antithrombin levels, the presence of signs of increased consumption, the underlying disorder, and the severity of the patient's clinical condition. The dose and frequency of administration must always be based on clinical efficacy and laboratory tests in each individual case.

The number of antithrombin units administered is expressed in International Units (IU), in relation to the current World Health Organization (WHO) standard for antithrombin. Plasma antithrombin activity is expressed as a percentage (relative to normal human plasma) or in International Units (relative to an international standard for antithrombin in plasma).

One International Unit (IU) of antithrombin activity is equivalent to the amount of antithrombin present in 1 mL of normal human plasma. The calculation of the required antithrombin dose is based on the empirical finding that 1 International Unit (IU) of antithrombin per kg of body weight increases plasma antithrombin activity by approximately 1.5%.

The initial dose is determined using the following formula:

Units required = body weight [kg] × (100 – current antithrombin activity [%]) × 2/3.

The antithrombin activity level to be initially achieved depends on the clinical status. When antithrombin replacement is indicated, the dose should be sufficient to reach the desired antithrombin activity level and maintain an effective level. The dose must be determined and monitored according to laboratory tests of antithrombin activity, which should be performed at least twice daily until the patient is stabilized, and thereafter once daily, preferably immediately before the next infusion. Dose adjustments should take into account both laboratory evidence of increased antithrombin consumption and the patient's clinical evolution. Antithrombin activity should be maintained above 80% during treatment, unless the clinical condition indicates a different efficacy level.

The usual initial dose in congenital deficiency is 30–50 IU/kg.

Therefore, the dose and frequency of administration, as well as the duration of treatment, should be adjusted according to biological data and clinical condition.

Paediatric population:

Kybernin P is not recommended for use in children under 6 years of age due to limited data.

Based on clinical experience, the use of antithrombin in the treatment of infant respiratory distress syndrome (IRDS) in premature infants cannot be recommended.

Instructions for correct administration of the preparation

General instructions

The lyophilized powder must be completely reconstituted under aseptic conditions with the accompanying solvent. A clear or slightly opalescent solution is obtained.

The appropriate diluent is 5% human albumin solution. For dilutions up to 1:5, the following may also be used: lactated Ringer's solution, physiological saline solution, 5% glucose solution, or polygeline.

The use of hydroxyethyl starches is not recommended as a solvent (for infusion), as a loss of antithrombin activity has been observed.

This medicinal product must not be mixed with other medicinal products in the same syringe/infusion set. Dopamine, dobutamine, and furosemide must not be administered through the same intravenous access.

The product must be administered intravenously. Maximum infusion rate: 4 mL/min.

Reconstitution

For proper handling of the double-ended Transofix® transfer device, follow the steps below: