Octaplex

LEAFLET INCLUDED IN THE PACKAGE: INFORMATION FOR THE USER

Octaplex, 500 IU, powder and solvent for solution for infusion
Human prothrombin complex
Octaplex, 1000 IU, powder and solvent for solution for infusion
Human prothrombin complex

You should carefully read the contents of the leaflet before using the medicine, as it contains important information for the patient.

• You should keep this leaflet, so you can read it again if you need to.
• In case of any doubts, you should consult a doctor, pharmacist, or nurse.
• This medicine has been prescribed to a specific person. It should not be given to others. The medicine may harm another person, even if the symptoms of their illness are the same.
• If the patient experiences any side effects, including any side effects not listed in this leaflet, they should tell their doctor, pharmacist, or nurse. See section 4.

Table of contents of the leaflet:

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

1. WHAT IS OCTAPLEX AND WHAT IS IT USED FOR

Octaplex belongs to a group of medicines called coagulation factors. It contains human vitamin K-dependent coagulation factors II, VII, IX, and X.
Octaplex is used to treat and prevent bleeding:

• caused by treatment with vitamin K antagonists (such as warfarin). These medicines block the action of vitamin K and cause a deficiency of vitamin K-dependent coagulation factors. Octaplex is used when rapid correction of the deficiency is required;
• in patients born with a deficiency of vitamin K-dependent coagulation factors II and X. It is administered when the purified product of the specific coagulation factor is not available.

2. IMPORTANT INFORMATION BEFORE USING OCTAPLEX

When not to use Octaplex:

• if the patient is allergic to any of the components of this medicine (listed in section 6),
• if the patient has an allergy to heparin or has ever had a decrease in platelet count after heparin.
• if the patient has an IgA deficiency with the presence of anti-IgA antibodies.

Warnings and precautions

• It is recommended to consult a specialist with experience in treating coagulation disorders while receiving Octaplex.
• In patients with acquired vitamin K-dependent coagulation factor deficiency (e.g., caused by treatment with vitamin K antagonists), Octaplex should only be used when rapid correction of the prothrombin complex level is necessary, such as in cases of major bleeding or emergency surgery. In other cases, reducing the dose of vitamin K antagonists and/or administering vitamin K is usually sufficient.
• Patients treated with vitamin K antagonists (such as warfarin) may have an increased risk of thrombosis. In such cases, treatment with Octaplex may increase this risk.
• In congenital deficiency of a specific vitamin K-dependent coagulation factor, the specific product of that coagulation factor should be used if available.
• In case of an allergic reaction or anaphylaxis, the infusion should be stopped immediately and appropriate treatment should be administered.
• There is a risk of thrombosis or disseminated intravascular coagulation (a serious condition characterized by the formation of blood clots throughout the body) in patients receiving Octaplex (especially when it is administered regularly). Patients receiving human prothrombin complex should be closely monitored for signs and symptoms of disseminated intravascular coagulation and thrombosis. This is especially important in patients with a history of coronary artery disease, liver disease, patients awaiting surgery, and when Octaplex is administered to small children.
• There are no available data on the use of Octaplex in cases of perinatal bleeding associated with vitamin K deficiency in newborns.

Viral safety

• In the case of medicinal products derived from human blood or plasma, appropriate methods are used to prevent the transmission of infections to patients. These include strict selection of blood and plasma donors to eliminate infected carriers and testing of individual donations and plasma pools for specific viral markers. Manufacturers of these products also include appropriate methods in the manufacturing process to inactivate or remove viruses. Despite this, in the case of administering products derived from human blood or plasma, the possibility of transmitting an infectious agent cannot be completely excluded. This also applies to infections caused by unknown or new viruses or other types of infections. The methods used are considered effective against enveloped viruses such as human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV). The methods used may have limited effectiveness against non-enveloped viruses such as hepatitis A virus (HAV) or parvovirus B19. Parvovirus B19 can be dangerous for pregnant women (fetal infection) and for patients with immune deficiencies or suffering from certain types of anemia (e.g., sickle cell anemia or hemolytic anemia). It is recommended to record the name and batch number of the product in case of each administration of Octaplex to associate it with the administered batch.
• Vaccinations (against viral hepatitis A and B) are recommended in case of regular/repeated administration of prothrombin complex products derived from human plasma.

Children and adolescents

Data on the use of Octaplex in children and adolescents are not available.

Octaplex and other medicines

Octaplex should not be mixed with other medicinal products.
Octaplex neutralizes the effect of treatment with vitamin K antagonists, but no interactions with other medicinal products are known.
Octaplex may affect the results of coagulation tests that are dependent on heparin.
The patient should tell their doctor or pharmacist about all medicines they are currently taking or have recently taken, as well as any medicines they plan to take.

Pregnancy and breastfeeding

Octaplex should be used during pregnancy and breastfeeding only if it is strictly necessary. Before using the product, the patient should consult their doctor or pharmacist.

Driving and using machines

The effect of Octaplex on the ability to drive vehicles and operate machinery is not known.

Important information about some ingredients of Octaplex

• Heparin may cause allergic reactions and a decrease in the number of blood cells responsible for blood clotting. Patients with known heparin-induced allergic reactions in the past should avoid using heparin-containing products.
• The medicine contains 75-125 mg (vial of 500 IU) or 150-250 mg (vial of 1000 IU) of sodium (the main component of common salt) in each vial. This corresponds to 3.8-6.3% or 7.5-12.5% of the maximum recommended daily intake of sodium in the diet for adults.

3. HOW TO USE OCTAPLEX

Treatment with Octaplex should be started under the supervision of a specialist in the treatment of coagulation disorders.

• First, the powder should be dissolved in water for injections.
• Then, the solution should be administered intravenously.

The dose of Octaplex and the duration of treatment depend on:

• the severity of the disease;
• the site of bleeding, its severity, and
• the patient's general condition.

Use of a higher dose of Octaplex than recommended

In case of overdose, the risk of

• developing thrombotic complications (such as myocardial infarction and thrombosis in veins or lungs),
• disseminated intravascular coagulation (a serious condition characterized by the formation of blood clots throughout the body) increases.

4. POSSIBLE SIDE EFFECTS

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Common (may affect up to 1 in 10 people)
Blood clots in blood vessels.
Uncommon (may affect up to 1 in 100 people)
Anxiety, increased blood pressure, symptoms resembling asthma, hemoptysis, nosebleeds, burning at the injection site, thrombi in the device.
Rare (may affect up to 1 in 1,000 people)
Allergic reactions may occur. Rarely, temporary increases in liver test results (transaminases) are observed. In patients treated with Octaplex for replacement therapy, neutralizing antibodies (inhibitors) against any of the contained coagulation factors may develop. In case of the development of these inhibitors, substitution therapy will not be highly effective.
Very rare (may affect up to 1 in 10,000 people)
Cases of increased body temperature (fever) have been observed.
There is a risk of thrombosis after administration of this medicine.
Frequency not known (frequency cannot be estimated from the available data)
Severe allergic reactions and shock, hypersensitivity, shivering, heart failure, accelerated heart rate, circulatory disorders, decreased blood pressure, respiratory failure, respiratory disorders, nausea, urticaria, rash, chills.
The heparin contained in the preparation may cause a sudden decrease in the number of platelets in the blood. This is an allergic reaction called "heparin-induced thrombocytopenia type II". In rare cases, this decrease in platelet count may occur 6-14 days after the start of treatment in patients without prior hypersensitivity to heparin. In patients with known hypersensitivity to heparin, this change may occur within a few hours after the start of treatment.
Treatment with Octaplex should be discontinued immediately in patients showing such an allergic reaction. These patients should not be given heparin-containing products in the future.
Information on viral safety, see section 2.

Reporting side effects

If any side effects occur, including any side effects not listed in this leaflet, the patient should tell their doctor, pharmacist, or nurse. Side effects can be reported directly to the Department of Monitoring of Adverse Reactions to Medicinal Products of the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products,
Jerozolimskie Avenue 181C, 02-222 Warsaw,
phone: +48 22 49 21 301, fax: +48 22 49 21 309
e-mail: ndl@urpl.gov.pl.
Reporting side effects can help gather more information on the safety of the medicine.

5. HOW TO STORE OCTAPLEX

The medicine should be stored out of sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging. The expiry date refers to the last day of the specified month.
Do not store above 25°C. Do not freeze. Store in the original packaging to protect from light.
The powder should be dissolved only immediately before injection. The stability of the solution has been demonstrated for up to 8 hours at 25°C. However, to avoid contamination, the solution should be used immediately and only once.

6. CONTENTS OF THE PACKAGE AND OTHER INFORMATION

What Octaplex contains in the vial and after dissolution in 20 ml (500 IU)/40 ml (1000 IU) solvent

The active substances are:

The specific activity of the product is ≥ 0.6 IU/mg, expressed as factor IX activity.
The other ingredients are:
heparin, trisodium citrate dihydrate, water for injections.

What Octaplex looks like and what the package contains

Octaplex is a powder and solvent for solution for infusion. It is a hygroscopic, white or slightly colored powder or a brittle mass in a glass vial.
The solvent is water for injections supplied in a glass vial. The prepared solution is clear to slightly opalescent and may be colored.
Octaplex is sold in a single box containing:

• 1 vial with powder for solution for infusion
• 1 vial with solvent, water for injections
• 1 Nextaro transfer set.

Marketing authorization holder and manufacturer

Octapharma (IP) SPRL
Research Avenue 65
1070 Anderlecht
Belgium
To obtain more detailed information, please contact the local representative of the marketing authorization holder:
Octapharma Poland Sp. z o.o.
Domaniewska Street 39a
02-135 Warsaw
phone: (22) 415-51-42
Manufacturers:
Octapharma Pharmazeutika Produktionsges.m.b.H.
Oberlaaer Street 235
1100 Vienna
Austria
Octapharma Lingolsheim S.A.S.
72 Marshal Foch Street
67380 Lingolsheim
France

This medicinal product is authorized for marketing in the Member States of the European Economic Area under the following names:

Austria, Belgium, Bulgaria, Croatia, Cyprus, Denmark, Estonia, Finland, France, Germany, Hungary, Iceland, Ireland, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Slovenia, Slovakia, Spain, United Kingdom: Octaplex
Czech Republic, Sweden: Ocplex
Italy, Romania: Pronativ

Date of last revision of the leaflet: 06.07.2024 -------------------------------------------------------------------------------------------------------------------------

INFORMATION FOR MEDICAL STAFF

General information on the use of Octaplex is presented in section 3.
The following information is intended only for medical staff or healthcare professionals:

Instructions for treatment

Read all instructions and follow them!
During the procedures described below, sterility must be ensured!
The product dissolves quickly at room temperature.
The reconstituted solution should be clear or slightly opalescent. Do not use cloudy solutions or those containing particles.
Before administration, visually inspect the solution for particulate matter or discoloration.
After reconstitution, the solution should be used immediately.
Any unused product or used material should be disposed of in accordance with local regulations.

Dosage

Bleeding and prophylaxis of bleeding in patients treated with vitamin K antagonists:
The dose depends on the INR before treatment and on the body weight. The table shows approximate doses (in units/kg body weight of the reconstituted product).

The dose is determined based on a body weight of up to 100 kg. Therefore, in patients with a body weight above 100 kg, the maximum single dose (IU of factor IX) should not exceed 2,500 IU for INR values of 2 - <4, 3,500 IU for INR values of 4 - 6, and 5,000 IU for INR values of > 6.

• The dosing is calculated based on experimental data, and the recovery and duration of action may vary, so monitoring of INR during treatment is mandatory.

Bleeding and prophylaxis of bleeding during surgical procedures in congenital deficiencies of vitamin K-dependent coagulation factors II and X, when the specific coagulation factor product is not available:
The required dose is calculated based on experimental data, such that approximately 1 IU of factor II or X per kg body weight increases the activity of factor II or X in plasma by 0.02 and 0.017 IU/ml, respectively.

• Required amount = body weight (kg) x desired increase in factor X (IU/ml) x 60, where 60 (ml/kg) is the assumed recovery index.
• Required doses for factor II: Required amount = body weight (kg) x desired increase in factor II (IU/ml) x 50 If individual recovery values are known, they should be used for calculations.

Reconstitution instructions:

• 1. If necessary, bring the solvent (water for injections) and powder in closed vials to room temperature. This temperature should be maintained during reconstitution. If a water bath is used for warming, care should be taken to avoid contact between the water and the rubber stoppers or caps of the vials. The temperature of the water bath should not exceed 37°C.
• 2. Remove the "flip-off" caps from the vial with the powder and the vial with the solvent and disinfect the rubber stoppers accordingly.
• 3. Tear off the cap of the outer packaging of the Nextaro set. Place the vial with the solvent on a flat surface and hold it firmly. Without removing the outer packaging, place the blue part of the Nextaro set on top of the vial with the solvent and press firmly until it clicks (Fig. 1). Do not twist during connection! Holding the vial with the solvent, carefully remove the outer packaging of the Nextaro set, taking care to leave the Nextaro set firmly attached to the vial with the solvent (Fig. 2)

Fig. 2
Fig. 1

• 4. Place the vial with the powder on a flat surface and hold it firmly. Take the vial with the solvent with the attached Nextaro set and turn it upside down. Place the transparent white part of the Nextaro connector on top of the vial with the powder and press firmly until it clicks (Fig. 3). Do not twist during connection! The solvent flows automatically into the vial with the powder.

Fig. 3

• 5. With both vials still connected, gently rotate the vial with the powder until the product is dissolved. Octaplex dissolves quickly at room temperature, giving a clear to slightly blue solution. Unscrew the Nextaro set into two parts (Fig. 4).

Discard the empty vial with the solvent with the blue part of the Nextaro set.
Fig. 4
If the powder is not completely dissolved or a solid substance forms, do not use the product.

Infusion instructions:

As a precaution, the patient's pulse should be checked before and during the infusion of factor IX. If a significant increase in pulse occurs, the infusion rate should be slowed down or the administration should be stopped.

• 1. Connect a 20 ml (for a 500 IU vial) or 40 ml (for a 1000 IU vial) syringe to the luer lock connector on the white part of the Nextaro set. Turn the vial upside down and draw the solution into the syringe. After transferring the solution, hold the syringe plunger firmly (holding it down) and remove the syringe from the Nextaro set. Discard the Nextaro set and the empty vial.
• 2. Disinfect the injection site accordingly.
• 3. Administer the solution intravenously at a rate of 0.12 ml/kg/min (~3 units/kg/min), up to a maximum of 8 ml/min (~210 units/min), under aseptic conditions.

Blood should not enter the syringe due to the risk of forming fibrin clots.
The Nextaro set is intended for single use only.