Betafact 1000 Iu

Leaflet attached to the packaging: patient information

BETAFACТ 1000 IU
Human coagulation factor IX
Read the leaflet carefully before using the medicine, as it contains important information for the patient.
Keep this leaflet, so you can read it again if you need to.
In case of any doubts, consult a doctor or pharmacist.
This medicine has been prescribed to a specific person. Do not pass it on to others. The medicine may harm another person, even if the symptoms are the same.
If the patient experiences any side effects, including any side effects not listed in this leaflet, inform the doctor or pharmacist. See section 4.

Table of contents of the leaflet:

1. What is BETAFACТ 1000 IU and what is it used for
2. Important information before using BETAFACТ 1000 IU
3. How to use BETAFACТ 1000 IU
4. Possible side effects
5. How to store BETAFACТ 1000 IU
6. Package contents and other information

BETAFACТ 1000 IU is a medicine belonging to the group of antihemorrhagic medicines. The active substance is human coagulation factor IX. It is a protein that occurs naturally in the human body. The function of this protein is to ensure proper blood clotting and prevent prolonged bleeding.
BETAFACТ 1000 IU is used to compensate for the lack of coagulation factor IX, thereby preventing and treating bleeding (hemorrhages) in patients with hemophilia B.
Hemophilia B is a hereditary disease associated with a lack of protein called coagulation factor IX. This deficiency leads to blood clotting disorders.

2. Important information before using BETAFACТ 1000 IU

When not to use BETAFACТ 1000 IU:

• If the patient is allergic to human coagulation factor IX or any of the components of this medicine (see section 6).
• If the patient has a severe allergic reaction (e.g., swelling, hives, difficulty breathing) after administration of human coagulation factor IX.

Warnings and precautions:

Before starting treatment with BETAFACТ 1000 IU, consult a doctor or pharmacist.
Caution should be exercised when using BETAFACТ 1000 IU in patients with liver or heart disease, as well as in patients with a risk of thrombosis.
In case of symptoms of an allergic reaction, administration of the medicine should be stopped immediately and a doctor should be consulted.
In case of symptoms of thrombosis (e.g., pain, swelling, redness of the limbs), a doctor should be consulted immediately.
Administration of BETAFACТ 1000 IU should be avoided in case of suspected acute respiratory distress syndrome (ARDS).

3. How to use BETAFACТ 1000 IU

This medicine should be used only under medical supervision.
Dosing and frequency of administration of BETAFACТ 1000 IU depend on:

• type and severity of bleeding
• location of bleeding
• patient's body weight
• level of coagulation factor IX in the patient's blood

BETAFACТ 1000 IU is administered intravenously.
Follow the doctor's instructions for dosing and administration of the medicine.

4. Possible side effects

Like all medicines, BETAFACТ 1000 IU can cause side effects, although not everybody gets them.

Frequent side effects (may occur in up to 1 in 10 patients):

• allergic reactions (e.g., itching, rash, hives)
• fever
• headache
• low blood pressure
• dizziness

Uncommon side effects (may occur in up to 1 in 100 patients):

• anaphylactic reactions (severe allergic reactions)
• shortness of breath
• chest pain
• nausea and vomiting
• diarrhea

Rare side effects (may occur in up to 1 in 1000 patients):

• thrombosis (blood clot formation)
• acute respiratory distress syndrome (ARDS)

5. How to store BETAFACТ 1000 IU

Store in a refrigerator at a temperature of 2°C to 8°C.
Do not freeze.
Store in the original packaging to protect from light.
Do not use the medicine after the expiry date stated on the packaging.

6. Package contents and other information

The packaging contains 1 vial of powder for solution for injection containing 1000 IU of human coagulation factor IX.
Additionally, the packaging contains:

• 1 ampoule of solvent (water for injection)
• 1 needle for solution preparation
• 1 syringe
• 1 filter

Not all packaging components may be available in every packaging.
The above information is general information only. In case of any doubts, consult a doctor or pharmacist.

Risk of blood clot formation

Due to the risk of improper blood clot formation (thromboembolic complications), the doctor should assess the potential benefits of treatment with human coagulation factor IX in the following situations:

• in patients with signs of fibrinolysis (fibrin degradation),
• in patients with disseminated intravascular coagulation (DIC),
• in patients undergoing surgical treatment,
• in patients with high coagulation risk,
• in patients with liver disease.

The doctor should refer the patient for a blood test to detect signs of these complications as soon as possible.
Risk of cardiovascular events
In case of cardiovascular risk factors in the patient, the doctor should assess the potential benefits of treatment with human coagulation factor IX.

Risk of allergic reaction

Due to the risk of allergic reaction (see section 4), the first administration of BETAFAC T 1000 IU must be performed under medical supervision, allowing for immediate treatment of an allergic reaction if necessary.
The doctor must inform the patient about possible symptoms of an allergic reaction (see section 4). In case of any such symptoms, administration should be stopped immediately and a doctor should be consulted to initiate appropriate treatment, depending on the type and severity of the reaction.
After repeated treatment with BETAFAC T 1000 IU, the patient's immune system may react to factor IX, producing inhibitors (antibodies against factor IX). The appearance of such inhibitors may reduce the effectiveness of treatment. The doctor must regularly perform blood tests to check for the presence of such inhibitors and determine their quantity.
A connection has been demonstrated between the presence of inhibitors and the occurrence of allergic reactions. To diagnose inhibitors, the doctor:

1. takes a blood sample from the patient,
2. performs appropriate laboratory tests,
3. evaluates the level of inhibitors.

If inhibitors are detected in the patient, the doctor should consult a hematologist to determine further treatment.

Other potential side effects

In rare cases, patients treated with human coagulation factor IX may develop neutralizing antibodies against factor IX. The presence of such antibodies may reduce the effectiveness of treatment.
In case of symptoms of an allergic reaction, administration of the medicine should be stopped immediately and a doctor should be consulted.

Accurate selection of blood and plasma donors based on tests and medical history to exclude donors at risk of infection.

Checking each donated blood sample and plasma pool for viruses and infectious agents.
Including in the manufacturing process of blood or plasma products procedures that inactivate viruses.
Despite the use of preventive measures when administering medicinal products derived from human blood or plasma, the risk of transmitting infectious agents cannot be completely excluded. This applies to all unknown or newly emerging viruses and other types of infections.
Measures taken during the manufacture of BETAFACT 1000 IU are considered effective against enveloped viruses, such as human immunodeficiency virus (HIV), hepatitis B virus, and hepatitis C virus.
The measures taken may have limited applicability in the case of non-enveloped viruses, such as hepatitis A virus and parvovirus B19. Infection with parvovirus B19 can have a severe course in pregnant women (fetal infection) and in individuals with impaired hemolytic function.

Vaccinations

The doctor may recommend that the patient be vaccinated against hepatitis A or B if they regularly/repeatedly receive products containing factor IX derived from human plasma.

Recording the batch number of the medicine

It is strongly recommended that when administering a dose of BETAFACT 1000 IU to a patient, the name and batch number of the medicine be recorded to associate the patient with the specific product batch.

Children

The warnings and precautions mentioned apply to both adults and children.

BETAFACT 1000 IU and other medicines

Inform the doctor or pharmacist about all medicines the patient is currently taking, as well as medicines taken in the past. This includes prescription medicines, over-the-counter medicines, and herbal medicines.

Contraindications

BETAFACT 1000 IU should not be used in the following cases:

• Hypersensitivity to human coagulation factor IX or any of the excipients.
• Severe allergic reactions (e.g., hives, angioedema, dyspnea, hypotension) after administration of a product containing factor IX.

Particular caution should be exercised when using BETAFACT 1000 IU in the following cases:

1. In patients who have developed antibodies against factor IX.
2. In patients with severe liver dysfunction or liver disease with impaired coagulation factor production.
3. In patients with circulatory disorders, such as pulmonary embolism or myocardial infarction.
4. In patients with a risk of thrombosis.

In case of symptoms of an allergic reaction, administration of the medicine should be stopped immediately and a doctor should be consulted.
Caution should be exercised when using the medicine in patients treated with warfarin or other anticoagulant medicines.
In case of fever, joint pain, rash, or other flu-like symptoms after administration of the medicine, consult a doctor.

BETAFRACT 1000 IU contains sodium

The medicine contains approximately 2.6 mg of sodium per 1 ml of product (52 mg per 20 ml vial). This should be taken into account if the patient is on a sodium-free or low-sodium diet.

BETAFRACT 1000 IU contains heparin

The medicine may cause an allergic reaction and a decrease in blood cell count, which can affect the blood clotting process.

3. How to use BETAFRACT 1000 IU

Treatment should be initiated by a doctor with experience in caring for patients with hemophilia B. This medicine should always be used in accordance with the doctor's instructions. In case of doubts, consult a doctor.

Dosing

The appropriate dose and frequency of administration depend on:

• body weight,
• severity of hemophilia,
• location and severity of bleeding,
• overall health condition,
• and, in specific cases, the procedure the patient will undergo (e.g., surgery, tooth extraction, etc.).

The doctor will recommend blood tests for the patient during treatment to monitor:

• factor IX concentration,
• presence of factor IX inhibitors.

Based on the results of such tests, the doctor may decide to change the dose size and frequency of injections.
The appropriate dose is expressed in units (IU).

Frequency of administration

The doctor will inform the patient how often to administer BETAFRACT 1000 IU.
The doctor will adjust the frequency of administration based on the severity of bleeding and the effectiveness of treatment.
At the end of this leaflet, in the section for medical staff, there is a table describing the frequency of administration and duration of treatment in different situations.

Method and route of administration

The medicine should be administered as an intravenous infusion after reconstitution using the provided solvent.

Indications

The medicine should be used in accordance with the doctor's instructions. Betafract 1000 IU is intended for:

• immediate medical attention is required,
• prevention and treatment of bleeding in patients with hemophilia B.

Memory of BETAFACET 1000 IU administration

Do not use a double dose to make up for a missed dose.
In case of any further doubts about using this medicine, consult a doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

• Hypersensitivity or allergic reaction occurs rarely. In some cases, such reactions can lead to severe allergic conditions.
• Allergic reactions may occur in case of inhibitor formation against factor IX and may affect kidney function (see section 2 "Risk of allergic reaction").

Possible signs of allergic reactions include:

• swelling of the face or throat,
• burning sensation and tingling at the injection site,
• chills,
• redness,
• itching and rash,
• low blood pressure,
• severe weakness (lethargy),
• nausea (nausea), vomiting,
• anxiety,
• rapid heartbeat (tachycardia),
• feeling of chest tightness,
• wheezing (similar to asthma).

In case of any such symptoms, treatment should be stopped immediately and a doctor should be consulted to initiate appropriate treatment, depending on the type and severity of the reaction.
During clinical trials with BETAFACET 1000 IU, the following side effects were observed, which may occur rarely (may occur in 1 to 1,000 patients):

• hypersensitivity and allergic reactions (see sections 2 and 4),
• headache,
• itching,
• nausea (nausea),
• injection site reactions (malaise, chest pain),
• allergic reaction at the injection site.

During the post-marketing period, two cases of neutralizing antibody formation (inhibitors) were reported - one patient did not respond to BETAFACET 1000 IU and one patient was treated with BETAFACET 1000 IU.

Side effects listed below were not observed during clinical trials with BETAFAC T 1000 IU, but were observed in patients taking a medicine from the same group as BETAFAC T 1000 IU:

Blood clots
Blood clots can form during treatment with low-purity factor IX products. They can:

• block blood flow and oxygen supply to the heart muscle, leading to a heart attack.
• block blood flow and oxygen supply to the lungs, leading to a life-threatening condition - pulmonary embolism.
• cause venous thrombosis (thrombophlebitis).
• cause blood clots in blood vessels throughout the body (disseminated intravascular coagulation).

BETAFAC T 1000 IU is a high-purity factor IX product and is rarely associated with such an effect.

• Inhibitor formation
• Patients taking factor IX products may develop antibodies against factor IX (so-called inhibitors - see section 2).
• During clinical trials with BETAFAC T 1000 IU, no such antibodies were observed in 11 previously untreated patients.

Reporting side effects

If any side effects occur, including any side effects not listed in the leaflet, inform the doctor, pharmacist, or nurse. Side effects can be reported directly to the Department of Adverse Reaction Monitoring of Medicinal Products, Medical Devices, and Biocides
02-222 Warsaw, Jerozolimskie Avenue 181C
tel 22 4921 301
fax 22 4921 309
email: adl@urpl.gov.pl
By reporting side effects, more information can be collected on the safety of the medicine.

5. How to store BETAFAC T 1000 IU

Store the medicine in a place inaccessible to children.
Store in a refrigerator at a temperature of 2-8°C. Do not freeze.
Do not use after the expiry date stated on the packaging.
Before reconstituting with water for injection, thaw the frozen product at room temperature (max. 25°C).
After the first reconstitution with water for injection, administer the solution to the patient immediately.
Do not use the solution if it has been left for more than 3 hours after reconstitution. The solution should be used once only.
Protect from light.
Store in the original packaging to protect from light.
The medicine should be used in accordance with the doctor's instructions.

6. BETAFAC T 1000 IU package contents and other information

The active substance is human coagulation factor IX with a concentration of 50 IU/ml after reconstitution. One vial contains 1000 IU/20 ml of human coagulation factor IX after reconstitution.
The specific activity of BETAFACT 1000 IU is approximately 110 IU/mg of total protein.
Other ingredients are:
In the powder: sodium chloride, sodium heparin, lysine hydrochloride, arginine, sodium citrate, and
In the solvent: water for injection (see section 2).
What BETAFACT 1000 IU looks like and what the package contains
BETAFACT 1000 IU is available as a powder and solvent for solution for injection (in 250 IU/5 ml vials) with a reconstitution set and a needle with a filter. BETAFACT 1000 IU is available in single packs.
Marketing authorization holder and manufacturer
LFB BIOMEDICAMENTS
3, avenue des Tropiques
ZA de Courtaboeuf
91940 Les Ulis
FRANCE
Phone: +33 (1) 69 82 70 10
This medicinal product is authorized in the Member States of the European Economic Area under the following names:

• Austria, Netherlands: BETAFACT 50 IU/ml
• Czech Republic, Greece, Slovakia: BETAFACT 50 IU/ml
• France, Portugal: BETAFACT 50 IU/ml
• Spain: BETAFACT 50 UI/ml, powder and solvent for solution for injection
• Germany: BETAFACT 1000 IU
• Poland: BETAFACT 1000 IU
• Romania: BETAFACT 1000 IU/ml, powder and solvent for solution for injection
• Hungary: BETAFACT 1000 IU/ml

Date of last revision of the leaflet:
October 2013
Information about this medicine can be found on the website of the Agency for Medicinal Products
3, avenue des Tropiques
ZA de Courtaboeuf
91940 Les Ulis
FRANCE

Indications

During treatment, it is recommended to determine the factor IX concentrations to determine the dose and frequency of administration. In individual patients, the response to factor IX may vary. The biological half-life and recovery time may also vary. The dose determined based on body weight may need to be adjusted in patients who are underweight or overweight. In the case of major surgical procedures, it is necessary to closely monitor the substitution treatment based on coagulation analysis (factor IX activity in plasma).

Dosing

The dose and duration of substitution treatment depend on the severity of factor IX deficiency, the location and severity of bleeding, and the patient's clinical condition.
The number of units of factor IX administered is expressed in international units (IU), which refer to the current World Health Organization (WHO) standard for factor IX products. Factor IX activity in plasma is expressed as a percentage value (relative to normal human plasma values) or in international units (relative to the International Standard for factor IX in plasma).
One international unit (IU) of factor IX activity corresponds to the amount of factor IX in one milliliter of normal human plasma.

Treatment according to needs

The required dose of factor IX is based on the empirical finding that one international unit (IU) of factor IX per kilogram of body weight increases the factor IX activity in plasma by 1.08% of the normal value. The required dose is determined using the formula:
Number of units to be administered =
body weight (kg) x desired increase in factor IX activity (%) / (IU/ml) x 0.93
The administered amount and frequency of administration should be adjusted according to the clinical effectiveness in individual cases.
In the case of planned surgical procedures, it should be taken into account that the postoperative factor IX level should be maintained at a level of ≥ 60% (IU/ml). Monitoring should be performed at regular intervals, especially in the first days after the procedure. Regular monitoring of factor IX levels is recommended.

Prophylaxis

Long-term regular administration of factor IX may reduce the frequency of bleeding. In patients with severe hemophilia B, prophylaxis should be started as early as possible, preferably before the first bleeding episodes.
The dose and frequency of administration should be adjusted individually for each patient, taking into account their age, body weight, severity of factor IX deficiency, frequency of bleeding, and physical activity.

Method of administration

The medicine should be administered intravenously. The infusion rate should be adjusted to the patient's tolerance. It is recommended to start the infusion at a low rate (e.g., 1 ml/min) and gradually increase it if no side effects occur.

Storage

Store in a refrigerator at a temperature of 2-8°C. Do not freeze.
Store in the original packaging to protect from light.

Expiry date

The expiry date is stated on the packaging. Do not use after the expiry date.

Surgical procedure

Minor surgical procedure, including tooth extraction 30–60 IU/kg every 24 hours, for at least one day, until wound healing.
Major surgical procedure 80–100 IU/kg Repeat the infusion every 8–24 hours to achieve adequate wound healing. Then, continue treatment for at least seven consecutive days to maintain factor IX activity at a level of 30–60% (IU/ml).
In some cases, higher doses than calculated may be necessary, especially for the initial dose.

Prophylaxis

As part of long-term prophylaxis against bleeding in patients with severe hemophilia B, the usual doses of factor IX are 20–40 IU/kg, administered every 3–4 days.
In some cases, especially in younger patients, it may be necessary to shorten the dosing intervals or use higher doses.
Patients previously treated
Currently available data are described in section 4.8, but no dosing recommendations can be provided.
Children and adolescents
During a clinical trial, 13 children under the age of sixteen were administered the medicinal product BETAFACt, using doses similar to those administered to adult patients (see also sections 4.4, 5.1, and 5.2).

Reconstitution:

The product should be reconstituted using water for injection, as described below.

• If necessary, warm both vials (powder and solvent) to room temperature.
• Wash your hands thoroughly with soap and warm water.
• Remove the protective cap from the vial with the powder and the solvent.
• Disinfect the surface of each stopper. Place the vial on a flat, clean surface.

Remove the semi-transparent cover from the reconstitution set and insert the needle into the solvent vial through the central hole in the stopper, while turning the needle.

• Remove the second cover from the other end of the reconstitution set.
• Holding both vials horizontally (with the air vent hole facing upwards), quickly insert the free end of the needle into the center of the stopper of the vial with the powder.
• Make sure the needle remains submerged in the solvent to avoid premature loss of vacuum.

Immediately position the set vertically, holding the solvent vial directly above the powder vial. This will allow the entire solvent to be transferred to the powder vial.
During the transfer of the solvent, direct the stream onto the entire surface of the powder. Ensure that all the solvent has been transferred.
The vacuum will disappear at the end of the transfer (sterile air).

• Remove the empty vial (solvent) from the reconstitution set.
• For a few minutes, gently rotate the vial with a rotational motion to prevent foam formation, until the powder is completely dissolved.

The solution should become clear and should be completely dissolved within 5 minutes. Do not use a cloudy solution or one containing particles.
Do not mix with other medicinal products.
Do not dilute the reconstituted product.

Storage after reconstitution

Use immediately. However, the chemical and physical stability of the solution has been demonstrated for:

Method of administration:

Draw the product into a sterile syringe using the provided needle with a filter.
Connect the syringe to the needle; remove any air from the syringe, disinfect the skin at the injection site, and insert the needle into a vein.
Administer intravenously as a single dose, not exceeding a flow rate of 4 ml/minute.