Feiba nf

Package leaflet: Information for the user

FEIBA NF, 2500 IU (50 IU/mL), powder and solvent for solution for injection
Anti-inhibitor coagulant complex
Please read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, please ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you personally. 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 any not listed in this leaflet, tell your doctor, pharmacist, or nurse. See section 4.

Contents of the leaflet

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

1. What FEIBA NF is and what it is used for

FEIBA NF is a medicine derived from human plasma that helps blood to clot in cases of deficiency or absence of certain clotting factors.
FEIBA NF is used to treat and prevent bleeding episodes in patients with hemophilia A complicated by the presence of factor VIII inhibitors and in patients with hemophilia B complicated by the presence of factor IX inhibitors.
Additionally, FEIBA NF may be used to treat and prevent bleeding in patients without hemophilia who have acquired inhibitors to factors VIII, IX, or XI.
FEIBA NF is also used in combination with factor VIII concentrate during long-term treatment aimed at complete and sustained elimination of factor VIII inhibitors, to enable regular treatment with factor VIII concentrate, as in patients without inhibitors.
In isolated cases, FEIBA NF has been used in patients with von Willebrand factor inhibitors.

2. Important information before using FEIBA NF

Inform the doctor if the patient has any allergies.
Inform the doctor if the patient is on a low-sodium diet.

When not to use FEIBA NF
FEIBA NF must not be used in the following situations if there is an alternative treatment available:

• if the patient is hypersensitive to the activated prothrombin complex concentrate anti-inhibitor or to any of the other components of this medicine (listed in section 6);
• if the patient has disseminated intravascular coagulation (DIC, consumption coagulopathy, a life-threatening condition associated with widespread blood clotting and formation of blood clots in vessels, leading to general depletion of coagulation factors);
• if the patient has acute thrombosis or embolism (including myocardial infarction).

See section "Warnings and precautions".

Warnings and precautions
Discuss with the doctor before starting treatment with FEIBA NF.
This medicine may cause allergic-type hypersensitivity reactions, including urticaria, angioedema, gastrointestinal symptoms, bronchospasm, and hypotension; these reactions may be severe and systemic (e.g. anaphylactic reaction with urticaria and angioedema, bronchospasm, and circulatory shock). Other infusion-related reactions such as chills, fever, and hypertension have also been reported.
If the first signs or symptoms of infusion-related reactions or hypersensitivity occur (see section 4), administration of this medicine must be stopped immediately and appropriate medical care initiated.
In patients suspected of hypersensitivity to FEIBA NF or any of its components, the doctor will decide whether to re-administer FEIBA NF only after careful consideration of risks and expected benefits and (or) when no response to treatment with other prophylactic therapies or alternative medicinal products can be expected.

Thromboembolic events, including disseminated intravascular coagulation (DIC), venous thrombosis, pulmonary embolism, myocardial infarction, and stroke, have occurred during treatment with FEIBA NF.
If the first signs or symptoms of thromboembolic events occur (see section 4), infusion must be stopped immediately and appropriate diagnostic and therapeutic measures initiated.

Some thromboembolic events occurred with high-dose FEIBA NF or in patients with other risk factors predisposing to thromboembolic events, including DIC, advanced atherosclerotic disease, crush injury, or sepsis. Concomitant use of recombinant factor VIIa may increase the risk of thromboembolic events. In patients with congenital or acquired hemophilia, the presence of such risk factors should always be considered.
FEIBA NF should be used with particular caution in patients at risk of DIC, arterial or venous thrombosis.

Cases of thrombotic microangiopathy have been reported in a clinical trial of emicizumab in which patients received FEIBA NF as part of breakthrough bleeding treatment.
In patients with hemophilia and presence of inhibitors or acquired inhibitors to coagulation factors, treatment with FEIBA NF may be associated with increased bleeding tendency and simultaneously increased risk of thrombosis.

Use of FEIBA NF is acceptable only when lack of response to treatment with appropriate coagulation factor concentrate is expected, e.g. in cases of high-titer inhibitors and life-threatening hemorrhage or bleeding risk (e.g. traumatic or postoperative), in the following situations:

• Disseminated intravascular coagulation (DIC);
• Liver impairment: due to delayed clearance of active coagulation factors in patients with impaired liver function, the risk of DIC is increased;
• Coronary heart disease, acute thrombosis and (or) embolism. See section "When not to use FEIBA NF".

For medicines produced from human blood or plasma, specific measures are taken to prevent transmission of infections to patients. These include careful selection of blood and plasma donors to ensure that those at risk of transmitting infections are excluded, and testing of individual blood donations and pooled plasma for viruses/infections. Manufacturers of these products also include steps in the processing of blood and plasma intended to inactivate or remove viruses. Despite these measures, when administering medicines produced from human blood or plasma, the possibility of transmitting infection cannot be completely excluded. This also applies to unknown or recently discovered viruses or other types of infections.

These measures are considered effective against enveloped viruses such as HIV (causing AIDS), hepatitis B virus, and hepatitis C virus, as well as the non-enveloped hepatitis A virus. The measures may have limited effectiveness against non-enveloped viruses such as parvovirus B19. Parvovirus B19 infection may be serious in pregnant women (fetal infection) and in individuals with immunodeficiency or increased erythropoiesis (e.g. hemolytic anemia).

In patients receiving factor VIII derived from human plasma regularly or repeatedly, appropriate vaccination (against hepatitis A and B) should be considered.

After administration of high doses of FEIBA NF, transient increases in passively transferred antibodies against hepatitis B surface antigen may result in false-positive results in serological tests.

The medicine contains isohemagglutinins, antibodies against red blood cells, which, when passively transferred, may affect the results of serological tests for antibodies against red blood cells, such as the antiglobulin test (Coombs test).

Each time a dose of FEIBA NF is administered to a patient, the name and batch number of the medicine must be clearly recorded to maintain information on batches used.

FEIBA NF and other medicines
Inform the doctor about all currently used or recently used medicines, including those available without a prescription.

Appropriate and well-controlled studies on combined or sequential treatment with FEIBA NF and recombinant factor VIIa, fibrinolytic inhibitors, or emicizumab have not been conducted (see "Warnings and precautions").

The possibility of thromboembolic events should be considered when systemic fibrinolytic inhibitors such as tranexamic acid and aminocaproic acid are used concomitantly with FEIBA NF. Therefore, fibrinolytic inhibitors should not be used for approximately 6 to 12 hours after administration of FEIBA NF.

Based on available in vitro data and clinical observations, a potential drug interaction leading to thromboembolic events cannot be excluded when recombinant factor VIIa is used concomitantly.

If treatment with FEIBA NF is considered after the patient has received emicizumab, the patient must be closely monitored by the treating physician.

As with all medicinal products containing coagulation factors, FEIBA NF must not be mixed with other medicines prior to administration, as this may adversely affect the efficacy and safety of the medicine.

It is recommended to flush the intravenous line with isotonic sodium chloride solution before and after administration of FEIBA NF.

Pregnancy, breastfeeding, and fertility
The doctor will decide whether FEIBA NF can be used during pregnancy or breastfeeding. Due to the increased risk of thrombosis during pregnancy, FEIBA NF should be used only under strict medical supervision and when clearly indicated.
Regarding the risk of parvovirus B19 infection, see "Warnings and precautions".

Driving and operating machinery
No effects on the ability to drive or operate machinery have been observed.

FEIBA NF contains sodium
The medicine contains 200 mg of sodium (main component of table salt) per vial. This corresponds to 10% of the maximum recommended daily intake of sodium in the diet for adults.

3. How to use FEIBA NF

The FEIBA NF lyophilized powder is reconstituted with the provided solvent and administered intravenously.
This medicine should always be used as directed by the physician. If in doubt, consult the
physician or pharmacist.
Treatment should be initiated and supervised by a physician experienced in managing
coagulation disorders.
The physician will determine the appropriate dose and frequency of administration individually for each patient, taking into account the severity of the coagulation disorder, location and extent of bleeding, and the patient's general condition and response to treatment. The prescribed dosage regimen must not be changed or discontinued without medical advice.
If the patient feels that the medicine is too strong or too weak, contact the physician or pharmacist.
Prior to administration, the medicine should be warmed to room temperature or body temperature if necessary.
FEIBA NF should be prepared immediately before use.
The reconstituted solution should be used immediately (the product does not contain preservatives).
Gently swirl until the powder is completely dissolved. Ensure that FEIBA NF is fully dissolved; otherwise, less FEIBA units will pass through the filter of the device.
Do not use solutions that are cloudy or contain sediment. Do not use solution from previously opened vials.
Use only the provided solvent (sterile water for injection) and reconstitution set.
If a different reconstitution and administration set is used other than the one supplied with the FEIBA NF package, ensure that a suitable filter with a pore size of at least 149 µm is used.
Do not use if the sterility maintenance system or the medicine packaging is damaged or compromised.
Record the administration of the medicine on the provided self-adhesive label.
Any unused medicine or waste material should be disposed of in accordance with local regulations.

Preparation of injection solution
Aseptic techniques must be followed throughout the entire procedure.

1. Bring the vial of solvent (sterile water for injection) to room temperature if necessary, e.g., by warming briefly in a water bath (max. 37°C).
2. Remove the protective caps from the vials containing the powder and solvent, and disinfect the rubber stoppers of both vials. Place the vials on a flat surface.
3. Open the BAXJECT II Hi-Flow device package by peeling off the paper lid without touching the inside (Fig. a). Do not remove the device from the package.
4. Turn the package upside down and insert the transparent plastic spike through the stopper of the solvent vial (Fig. b). Holding the package by the edges, remove the package from the BAXJECT II Hi-Flow device (Fig. c). Do not remove the blue cap from the BAXJECT II Hi-Flow device.
5. Invert the BAXJECT II Hi-Flow device connected to the solvent vial so that the solvent vial is positioned above the device. Insert the purple plastic spike through the stopper of the FEIBA NF powder vial. The vacuum will draw the solvent into the FEIBA NF powder vial (Fig. d).
6. Gently mix by swirling without shaking until the product is completely dissolved. Ensure that FEIBA NF is fully dissolved—otherwise, the active substance may not pass through the device filter.

Fig. a Fig. b Fig. c

Injection/Infusion
Maintain aseptic technique throughout the procedure.

1. Remove the blue cap from the BAXJECT II Hi-Flow device. Firmly connect the syringe to the BAXJECT II Hi-Flow (DO NOT DRAW AIR INTO THE SYRINGE). To ensure a secure connection between the syringe and the BAXJECT II Hi-Flow device, it is strongly recommended to use a syringe with a Luer-type tip (attach the syringe by turning clockwise until it stops) (Fig. e).
2. Invert the assembly so that the solution is on top. Draw the solution into the syringe by slowly pulling back the plunger, ensuring that the connection between the syringe and the BAXJECT II Hi-Flow device remains tight and that the syringe remains securely attached during the entire withdrawal process (Fig. f).
3. Disconnect the syringe.
4. If foam appears in the syringe, wait until the foam disappears. Slowly administer the solution intravenously using an infusion set (or a single-use injection needle). An infusion pump may be used to control the rate of administration.

Fig. d Fig. e Fig. f

Do not exceed a rate of 2 units of FEIBA per kg body weight per minute.
Overdose of FEIBA NF
Inform the physician immediately. Overdosing with FEIBA NF may increase the risk of
adverse effects such as thromboembolic events (blood clots that travel through blood vessels),
consumption coagulopathy (disseminated intravascular coagulation, DIC), or myocardial infarction.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
You should contact your doctor immediately if one or more of the following symptoms occur:

• Hypersensitivity reactions: rash, itchy rash (urticaria), itching, swelling of lips and tongue, wheezing, feeling of chest tightness, gastrointestinal symptoms, dizziness, sudden drop in blood pressure, chills, fever, hypertension, coma
• Disseminated intravascular coagulation (DIC): spontaneous bruising, petechiae, severe simultaneous bleeding (e.g. from wounds, injection sites, mucous membranes, genital tract), organ failure due to ischemia (in kidneys, for example: anuria or oliguria; in lungs - dyspnea, cough, hemoptysis; in brain - disorientation and concentration problems, seizures, disturbances of consciousness, coma)
• Venous thrombosis: pain and swelling of a limb, usually unilateral, increased warmth of the limb, subfebrile condition or fever
• Pulmonary embolism: significant changes in blood pressure or heart rate, difficulty breathing, cough or chest pain
• Myocardial infarction: chest pain which may radiate to the left shoulder or arm, jaw, epigastrium or back; dyspnea, palpitations, dizziness, fainting, weakness, restlessness, anxiety
• Stroke: sudden, severe headache, visual disturbances, unilateral drooping of the corner of the mouth, difficulty swallowing and speaking, impaired motor coordination and balance, drowsiness, disorientation, loss of consciousness

Frequent adverse reactions (may affect up to 1 in 10 people):

• Hypersensitivity
• Headache, dizziness
• Hypotension
• Rash
• Positive test result for antibodies against hepatitis B surface antigen, elevated fibrin D-dimer concentration

Adverse reactions of unknown frequency (cannot be estimated from available data):

• Disseminated intravascular coagulation (DIC), increased inhibitor titer
• Anaphylactic reaction (rapid-onset, life-threatening hypersensitivity reaction), itchy skin rash over the entire body (urticaria)
• Numbness of limbs (hypoesthesia), abnormal or reduced sensation (paresthesia), stroke (ischemic stroke, embolic stroke), somnolence, taste disturbances
• Heart attack (myocardial infarction), palpitations (tachycardia)
• Formation of blood clots (venous thrombosis, arterial thrombosis), which travel through blood vessels (thromboembolic events), increased blood pressure (hypertension), sudden flushing
• Pulmonary artery embolism (pulmonary embolism), narrowing of airways (bronchospasm), wheezing, cough, shortness of breath (dyspnea)
• Vomiting, diarrhea, abdominal discomfort, nausea
• Numbness of the face, facial swelling, swelling of the tongue and lips (angioedema), itchy rash over the entire body (urticaria), itching (pruritus)
• Pain at injection site, general malaise, feeling of warmth, chills, fever, chest pain, chest discomfort
• S drop in blood pressure

Symptoms of hypersensitivity reactions following administration of medicines derived from human plasma also include coma and restlessness.
Reporting of adverse reactions
If any adverse reactions occur, including any adverse reactions not listed in this leaflet, you should inform your doctor, pharmacist, or nurse. 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
Phone: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorization holder.
Reporting adverse reactions helps provide more information on the safety of this medicine.

5. How to store FEIBA NF

Keep this medicine out of the sight and reach of children.
Do not store above 25°C. Do not freeze.
Store the medicine in the outer packaging to protect from light.
Do not use this medicine after the expiry date stated on the packaging.
The expiry date refers to the last day of the stated month.
Medicines should not be disposed of via wastewater or household waste. Ask a pharmacist how to dispose of medicines no longer required. These measures help protect the environment.

6. Contents of the package and other information

What FEIBA NF contains
Powder

• The active substance is a coagulation factor complex anti-inhibitor factor VIII. After reconstitution in 50 ml of the solvent supplied in the pack (water for injections), 1 ml contains approximately 50 IU of coagulation factor complex anti-inhibitor factor VIII. One vial contains 2500 IU of factor VIII with bypassing activity and 1000–3000 mg of human plasma protein.
• FEIBA NF also contains factors II, IX, and X, mainly in non-activated form, and activated factor VII. Coagulation antigen factor VIII (F VIII C:Ag) is present at a concentration of up to 0.1 units per 1 unit of FEIBA. Kallikrein-kinin system factors are present only in trace amounts or are absent.
• Other components of the medicine are: sodium chloride and sodium citrate.

Solvent

• Water for injections

What FEIBA NF looks like and contents of the pack
The medicine is a lyophilized powder or a light solid substance, white or pale green in color.
The powder and solvent are supplied in glass vials closed with rubber stoppers.
The pH of the solution after reconstitution is between 6.8 and 7.6.
Pack size: 1 set
Contents of the pack:
1 vial containing 2500 IU FEIBA NF, closed with a rubber stopper
1 vial containing 50 ml water for injections, closed with a rubber stopper
1 BAXJECT II Hi-Flow - a needle-free transfer device used to transfer and mix the medicines contained in the two vials
1 single-use syringe
1 injection needle
1 butterfly needle (infusion set with butterfly needle)
Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder:
Takeda Pharma Sp. z o.o.
ul. Prosta 68
00-838 Warsaw, Poland
Tel: +48 22 306 24 47
[email protected]
Manufacturer:
Takeda Manufacturing Austria AG
Industriestrasse 67
1221 Vienna, Austria

Information intended exclusively for healthcare professionals:

Treatment should be initiated and supervised by a physician experienced in the management of
hemophilia.
Dosage
The dosage and duration of treatment depend on the severity of the coagulation disorder, location
and extent of bleeding, and the patient's clinical condition.
The dose and frequency of administration should always be adjusted according to the clinical
response in each individual case.
Generally, a dose of 50–100 IU FEIBA per kg body weight (b.w.) is recommended. However, the
single dose should not exceed 100 IU/kg b.w., nor should the maximum daily dose exceed 200
IU/kg b.w., unless the severity of bleeding justifies and warrants higher doses.
Due to patient-specific factors, the response to activated prothrombin complex concentrates with
bypassing activity may vary. In a given bleeding episode, if the response to one agent is inadequate,
consideration should be given to using another agent.
Children and adolescents
Experience with use in children under 6 years of age is limited; the dosing regimen, similar to that
in adults, should be adjusted according to the child's clinical condition.
1) Spontaneous hemorrhages
Hemarthrosis, muscle and soft tissue bleeding
For minor or moderate bleeding episodes, a dose of 50–75 IU/kg b.w. administered every 12 hours
is recommended. Treatment should continue until clear signs of clinical improvement are observed,
such as relief of pain, reduction of swelling, or joint mobilization.
For major muscle and soft tissue hemorrhages, such as retroperitoneal bleeding, a dose of 100
IU/kg b.w. every 12 hours is recommended.
Mucosal bleeding
A dose of 50 IU/kg b.w. every 6 hours is recommended, with close patient monitoring (observation
of the bleeding site, repeated hematocrit measurements). If bleeding persists, the dose may be
increased to 100 IU/kg b.w. The maximum daily dose of 200 IU/kg b.w. should not be exceeded.
Other severe hemorrhages
For severe bleeding episodes, such as central nervous system bleeding, a dose of 100 IU/kg b.w.
every 12 hours is recommended. In individual cases, FEIBA NF may be administered every 6
hours until clear clinical improvement is achieved. The maximum daily dose of 200 IU/kg b.w.
must not be exceeded!
2) Surgical procedures
Administer 50–100 IU/kg b.w. every 6 hours, taking care not to exceed the maximum daily dose.
3) Prophylaxis
Limited clinical data are available regarding the use of FEIBA NF for prophylaxis of bleeding in
hemophilia patients.

• Prophylactic treatment of bleeding in patients with high inhibitor titers and frequent bleeding episodes in whom immune tolerance induction (ITI) has failed or is not considered: A dose of 70–100 IU/kg b.w. every other day is recommended. If bleeding persists, the dose may be increased to 100 IU/kg b.w. daily, or gradually decreased.
• Prophylactic treatment of bleeding in patients with high inhibitor titers during immune tolerance induction (ITI): FEIBA NF may be administered concomitantly with factor VIII concentrates at doses of 50–100 IU/kg b.w. twice daily, until the factor VIII inhibitor titer decreases to <2 j.B.*

*1 Bethesda unit is defined as the amount of antibody that reduces factor VIII activity by 50% in normal fresh human plasma after 2 hours of incubation at 37°C.
Administration
See also section "FEIBA NF and other medicinal products" and section 3 of the package leaflet.
FEIBA NF should be administered slowly intravenously (no faster than 2 IU/kg b.w. per minute).
FEIBA NF should be prepared immediately before administration.
The solution should be used immediately (it contains no preservatives). Do not use the solution if it
is cloudy or contains particulate matter.
Do not use if the transfer device, the system maintaining its sterility, or its packaging is damaged
or compromised.
Any unused solution should be discarded according to applicable procedures.
Monitoring of treatment
Due to its complex mechanism of action, there is no direct method available for monitoring the
active substances.
In vitro laboratory tests used to assess treatment efficacy, such as aPTT, whole blood clotting
time, and thromboelastography (TEG), may not reflect clinical improvement. Therefore, attempts
to normalize these parameters by increasing FEIBA NF doses may be misleading and should be
avoided due to the risk of DIC caused by overdosage.
In cases of inadequate response to FEIBA NF treatment, platelet count should be determined, as
an adequate number of functionally intact platelets is essential for the efficacy of FEIBA NF.
Single doses exceeding 100 IU/kg b.w. and daily doses exceeding 200 IU/kg b.w. should not be
administered. Patients receiving more than 100 IU/kg b.w. must be monitored for the development
of DIC and/or acute coronary syndrome. High doses of FEIBA NF should be administered only for
the period necessary to control bleeding.
If significant changes in blood pressure, pulse rate, respiratory function, chest pain, or cough occur,
administration should be stopped immediately and appropriate diagnostic and therapeutic
measures should be initiated.
Laboratory findings indicative of DIC include decreased fibrinogen levels, reduced platelet count,
and presence of fibrin/fibrinogen degradation products (FDP).
Administration of FEIBA NF to patients with inhibitors may initially result in an anamnestic rise
in inhibitor levels. With continued administration of FEIBA NF, inhibitor levels may decrease over
time. Clinical and literature data indicate that the efficacy of FEIBA NF is not reduced.
During administration of FEIBA NF, patients with hemophilia complicated by the presence of
inhibitors or patients with acquired inhibitors of coagulation factors may experience both a
tendency to bleeding and an increased risk of thrombosis.
See also section "Warnings and precautions".
Detailed information about this medicinal product is available in the Summary of Product
Characteristics on the website of the Office for Registration of Medicinal Products, Medical Devices
and Biocidal Products.