Feiba 50 U/ml powder and solvent for solution for infusion

Patient Information Leaflet

Introduction

Patient Information Leaflet

FEIBA 50 U/ml powder and solvent for solution for infusion

Anti-inhibitor coagulant complex

Read this entire leaflet carefully before you start using this medicine, as 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 others, even if they have the same symptoms as you, because it may 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 this leaflet

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

1. What FEIBA is and what it is used for

FEIBA is a preparation made from human plasma that enables hemostasis, even when the levels of specific coagulation factors are reduced or absent.

FEIBA is used for the treatment and prophylaxis of bleeding episodes in patients with hemophilia A and inhibitor.

FEIBA is used for the treatment of bleeding episodes in patients with hemophilia B and inhibitor.

FEIBA is used for the treatment and prophylaxis of bleeding episodes in non-hemophilic patients with acquired factor VIII inhibitor.

In addition, FEIBA is used for prophylaxis during surgical procedures in patients with hemophilia A and inhibitor.

FEIBA can be used in all age groups.

2. What you need to know before using FEIBA

Inform your doctor if you have any known allergies.

Inform your doctor if you are on a low-sodium diet.

Do not use FEIBA

FEIBA should only be used under the following circumstances, for example, if due to very high inhibitor titers, no response is expected to treatment with the appropriate coagulation factor concentrate:

• if you are allergic (hypersensitive) to anti-inhibitor coagulant complex or to any of the other components of this medicine (listed in section 6).

• if you have disseminated intravascular coagulation (DIC). (DIC = consumption coagulopathy, a potentially life-threatening condition in which there is excessive blood clotting, with pronounced formation of blood clots in blood vessels. This leads to systemic consumption of coagulation factors.)

• in cases of acute myocardial infarction, thrombosis, and/or embolism: FEIBA should only be used in hemorrhagic episodes that are life-threatening.

Warnings and precautions

Talk to your doctor before starting to use FEIBA, as hypersensitivity reactions may occur, as with all plasma-derived products administered intravenously. To recognize an allergic reaction as early as possible, you should be aware that potential initial symptoms of a hypersensitivity reaction may include:

• erythema (skin redness)
• skin rash
• appearance of hives on the skin (urticaria)
• itching all over the body
• swelling of the lips and tongue
• difficulty breathing/dyspnea
• chest tightness
• general malaise
• dizziness
• drop in blood pressure

Other symptoms of hypersensitivity reactions to plasma-derived products include lethargy and fatigue.

If you notice any of these symptoms, you must stop administration immediately and contact your doctor immediately. The symptoms described may indicate anaphylactic shock. Severe symptoms require early emergency treatment.

Your doctor will only reuse FEIBA in patients with suspected hypersensitivity to the product or to any of its components after carefully weighing the expected benefit against the risk of re-exposure and/or the lack of response to another preventive treatment or alternative therapy.

• If you experience significant changes in blood pressure or pulse rate, difficulty breathing, coughing, or chest pain, you must stop administration immediately and contact your doctor. Your doctor will initiate appropriate diagnostic and therapeutic measures.
• In patients with hemophilia with inhibitors or acquired inhibitors to coagulation factors: during treatment with FEIBA, these patients may have an increased tendency to bleed and an increased risk of thrombosis simultaneously.

Thrombotic and thromboembolic events, including disseminated intravascular coagulation (DIC), venous thrombosis, pulmonary embolism, myocardial infarction, and stroke, have occurred during treatment with FEIBA. Concomitant use with recombinant factor VIIa may increase the risk of developing a thromboembolic event. Some of these thromboembolic events have occurred with high-dose FEIBA treatment.

In a study conducted by another company to evaluate emicizumab (a medication to prevent bleeding in patients with hemophilia A), some patients who experienced breakthrough bleeding were treated with FEIBA to control the bleeding, and some of these patients developed thrombotic microangiopathy (TMA). TMA is a serious and potentially life-threatening condition. When this condition occurs, the vascular wall may be damaged and clots may form in small blood vessels. In some cases, this can lead to kidney damage and damage to other organs. In case of breakthrough bleeding while on emicizumab prophylaxis, contact your hematologist or Hemophilia Treatment Center immediately.

When medicines derived from human plasma or blood are administered, certain measures must be taken to prevent transmission of infections to patients. Such measures include careful donor selection to exclude those at risk of being carriers of infectious diseases, testing for specific markers of infection in individual donations and plasma pools, and inclusion of manufacturing steps to eliminate/inactivate viruses. Despite these measures, when medicines derived from human blood or plasma are administered, the possibility of transmission of infectious agents cannot be completely excluded. This also applies to emerging or unknown viruses and other types of infections.

These measures are considered effective against enveloped viruses such as human immunodeficiency virus (HIV), hepatitis B virus, and hepatitis C virus, as well as against non-enveloped hepatitis A virus. However, the measures taken may have limited effectiveness against non-enveloped viruses such as parvovirus B19.

Parvovirus B19 infection may be severe for pregnant women (fetal infection) and for individuals with weakened immune systems or patients with certain types of anemia (e.g., sickle cell disease or hemolytic anemia).

Your doctor may recommend vaccination against hepatitis A and hepatitis B if you are receiving plasma-derived products for Factor VIII inhibitors on a regular or repeated basis.

After administration of high doses of FEIBA, the transient increase in passively transferred hepatitis B surface antibodies may lead to misinterpretation of serological test results as positive.

FEIBA is a plasma-derived product and may contain substances that react when infused into patients, leading to the presence of isohemagglutinins (antibodies that cause agglutination of red blood cells from another person). This process may lead to misinterpretation of blood test results.

It is strongly recommended that each time a dose of FEIBA is administered, the name of the medicine and the batch number used should be recorded to maintain a record of the batches used.

Children

Experience in children under 6 years of age is limited; the same dosing regimen as in adults should be adapted according to the child's clinical condition.

Use of FEIBA with other medicines

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

Adequate and well-controlled studies on the combined or sequential use of FEIBA with recombinant factor VIIa, antifibrinolytics, or emicizumab have not been conducted. When systemic antifibrinolytics such as tranexamic acid and aminocaproic acid are used during treatment with FEIBA, the possibility of thromboembolic events should be considered. Therefore, antifibrinolytics should not be used until approximately 6 to 12 hours after administration of FEIBA.

Based on available in vitro data and clinical observations, a potential drug interaction with concomitant use of recombinant factor VIIa, which could potentially lead to a thromboembolic event, cannot be excluded.

Inform your doctor if you are to be treated with FEIBA after having received emicizumab (a medication to prevent bleeding in patients with hemophilia A), as certain specific warnings and precautions must be considered. Your doctor will need to monitor you closely.

As with all products used for blood coagulation, FEIBA must not be mixed with other medicines prior to administration, as this may impair the efficacy and tolerability of the product. It is advisable to flush the intravenous line with isotonic saline solution before and after administration of FEIBA.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to become pregnant, consult your doctor or pharmacist before using this medicine.

Your doctor will decide whether FEIBA can be used during pregnancy and breastfeeding. Due to the increased risk of thrombosis during pregnancy, FEIBA should only be administered under close medical supervision and only if clearly indicated. For information on the risk of infection with parvovirus B19, see section Warnings and precautions.

Driving and use of machines

There is no indication that FEIBA may affect the ability to drive or operate machinery.

FEIBA contains sodium

500 U

This medicine contains approximately 40 mg of sodium (main component of table/cooking salt) per vial. This corresponds to 2% of the maximum daily sodium intake recommended for an adult.

1000 U

This medicine contains approximately 80 mg of sodium (main component of table/cooking salt) per vial. This corresponds to 4% of the maximum daily sodium intake recommended for an adult.

2500 U

This medicine contains approximately 200 mg of sodium (main component of table/cooking salt) per vial. This corresponds to 10% of the maximum daily sodium intake recommended for an adult.

3. How to use FEIBA

Reconstitute the lyophilized FEIBA powder with the solvent provided and administer the solution intravenously.

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

Your doctor will determine the frequency and dose required for you personally, taking into account the severity of the blood coagulation disorder, the location and extent of bleeding, and your clinical condition and response to the preparation. Do not change the dosage prescribed by your doctor and do not stop administering the preparation.

If you feel that the effect of FEIBA is too strong or too weak, consult your doctor or pharmacist.

Warm the product to room temperature or body temperature before administration, if necessary.

FEIBA must be reconstituted immediately before use. The solution must be used immediately (since the preparation does not contain preservatives).

Gently swirl until all the product is dissolved. Ensure that FEIBA is completely dissolved, as otherwise fewer units of FEIBA will pass through the filter of the equipment.

Solutions that appear cloudy or contain deposits must be properly discarded.

Do not reuse opened containers.

Use only the water for injection and reconstitution equipment provided in the package.

If other equipment different from that provided is used, ensure that an appropriate filter with a pore size of at least 149 µm is used.

Do not use the product if its sterile barrier system or container is damaged or shows any signs of deterioration.

Do not refrigerate after reconstitution.

After complete reconstitution of FEIBA, the injection or infusion must begin immediately and be completed within 3 hours of reconstitution.

Disposal of unused medicine and all materials that have come into contact with it must be carried out in accordance with local regulations.

[For the leaflet for administration with needles]

Reconstitution of the powder for the preparation of a solution for infusion with needles:

An aseptic technique must be used throughout the procedure.

1. Warm the unopened solvent vial (water for injection) to room temperature or up to a maximum of +37 °C, if necessary.

2. Remove the protective caps from the vial containing the powder and the vial containing the solvent (Figure A), and disinfect the rubber stoppers of both vials.

3. Twist to open the protective cap from one end of the transfer needle provided, remove it, and insert the needle through the rubber stopper of the solvent vial (Figures B and C).

4. Remove the protective cap from the other end of the transfer needle, taking care not to touch it.

5. Invert the solvent vial and insert the free end of the transfer needle through the rubber stopper of the powder vial (Figure D). The vacuum in this vial will draw in the solvent.

6. Separate the two vials by removing the transfer needle from the powder vial (Figure E). Gently swirl the powder vial to accelerate dissolution.

7. Once the powder is completely dissolved, insert the air-venting needle (Figure F) and any foam formed will disappear. Remove the air-venting needle.

Infusion:

An aseptic technique must be used throughout the procedure.

1. Twist to remove the protective cap from one end of the provided filter needle; remove and attach the needle to the sterile disposable syringe. Draw the solution into the syringe (Figure G).
2. Detach the filter needle from the syringe and administer the solution slowly intravenously using the infusion equipment provided (or the disposable needle provided).

Figure A Figure B Figure C Figure D Figure E Figure F Figure G

[For the leaflet for administration with BAXJECT II-Hi-Flow ]

Reconstitution of the powder for the preparation of a solution for infusion using the BAXJECT II Hi-Flow device:

1. Warm the unopened solvent vial (water for injection) to room temperature or up to a maximum of 37°C, if necessary, for example, by using a water bath for several minutes.

2. Remove the protective caps from the powder vial and the solvent vial, 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 removing the protective foil without touching the contents (Figure a). Do not remove the device from the packaging.

4. Turn the package over and insert the transparent plastic tip through the rubber stopper of the solvent vial (Figure b). Now remove the BAXJECT II Hi-Flow device from its packaging (Figure c). Do not remove the blue protective cap from the BAXJECT II Hi-Flow device.

5. With the BAXJECT II Hi-Flow device attached to the solvent vial, invert the system so that the solvent vial is on top. Insert the purple plastic tip of the BAXJECT II Hi-Flow device through the stopper of the FEIBA vial. The vacuum will cause the solvent to enter the FEIBA vial (Figure d).

6. Gently swirl, without shaking, the entire system until all the powder is dissolved. Make sure FEIBA is completely dissolved; otherwise, the active ingredient may be retained in the filter of the device.

Figure a	Figure b	Figure c

Infusion

Use aseptic technique throughout the procedure!

1. Remove the blue protective cap from the BAXJECT II Hi-Flow device. Firmly connect the syringe to the BAXJECT II Hi-Flow device. DO NOT INTRODUCE AIR INTO THE SYRINGE. (Figure e). It is strongly recommended to use a Luer Lock syringe to ensure a secure connection between the syringe and the BAXJECT II Hi-Flow device (rotate the syringe clockwise until it stops).

2. Invert the system so that the dissolved product is at the top. Draw the dissolved product into the syringe by slowly pulling back on the plunger, ensuring that the secure connection between the BAXJECT II Hi-Flow device and the syringe is maintained throughout the process while pulling back on the syringe plunger (Figure f).

3. Disconnect the syringe.

4. If foam appears in the syringe, wait for the foam to dissipate. Administer the solution slowly by intravenous infusion using the provided infusion set (or a disposable needle).

Figure d	Figure e	Figure f

Do not exceed an infusion rate of 2 IU of FEIBA/kg per minute.

If you use more FEIBA than you should

Inform your doctor immediately. Overdosing on FEIBA may increase the risk of adverse effects such as thromboembolism (formation of a blood clot with redness in blood vessels), disseminated intravascular coagulation (DIC), or myocardial infarction. Some of the reported thromboembolic events occurred with doses exceeding 200 IU/kg/day or in patients with other risk factors for thromboembolic events.

If signs or symptoms of a thromboembolic event are observed, the infusion must be stopped immediately and appropriate diagnostic and therapeutic measures should be taken.

4. Possible adverse effects

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

Frequent adverse effects (may affect up to 1 in 10 patients)

Hypersensitivity, headache, dizziness, hypotension, skin rash, positive hepatitis B surface antibodies.

Adverse effects with unknown frequency (cannot be estimated from available data)

Blood and lymphatic system disorders: disseminated intravascular coagulation (DIC), increased inhibitor titre

Immune system disorders: anaphylactic reactions, generalized skin rash (urticaria)

Nervous system disorders: numbness or tingling sensation in the limbs (hypoesthesia), abnormal or reduced sensation (paresthesia), stroke (thrombotic event, embolic event), somnolence, altered sense of taste (dysgeusia).

Cardiac disorders: heart attack (myocardial infarction), rapid or irregular heartbeat (palpitations, tachycardia)

Vascular disorders: blood clot formation with redness of blood vessels (thromboembolic events, venous and arterial thrombosis), increased blood pressure (hypertension), flushing.

Respiratory, thoracic and mediastinal disorders: blockage of the pulmonary artery (pulmonary embolism), airway obstruction (bronchospasm), chest wheezing, cough, difficulty breathing (dyspnea).

Gastrointestinal disorders: vomiting, diarrhoea, abdominal discomfort, feeling of illness (nausea)

Skin and subcutaneous tissue disorders: numbness in the face, swelling of the face, tongue and lips (angioedema), generalized skin rash (urticaria), itching (pruritus).

General disorders and administration site conditions: pain at injection site, general malaise, feeling of warmth, chills, fever, chest pain, chest discomfort.

Investigations: drop in blood pressure, increased blood fibrin D-dimer levels.

Rapid intravenous infusion may cause sharp pain and a tingling sensation in the face and limbs, as well as a drop in blood pressure.

Cases of myocardial infarction have been reported after administration of doses exceeding the maximum daily dose and/or prolonged administration and/or in the presence of thromboembolic risk factors.

Reporting of adverse effects

If you experience any type of adverse effect, consult your doctor, even if it is a possible adverse effect not listed in this leaflet. You may also report them directly via the Spanish Pharmacovigilance System for Human Medicinal Products: www.notificaram.es

By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of FEIBA

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

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

Store in the original packaging to protect from light.

Do not use this medicine after the expiry date stated on the label and container. The expiry date is the last day of the month indicated.

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 FEIBA

Powder

• The active substance per vial is anti-inhibitor coagulant complex.

• 1 ml contains 50 U of anti-inhibitor coagulant complex.

• FEIBA 50 U/ml is available in three presentations:

• The 500 U presentation of FEIBA contains 500 U (units) of anti-inhibitor coagulant complex in 200 – 600 mg of human plasma protein.

• The 1000 U presentation of FEIBA contains 1000 U (units) of anti-inhibitor coagulant complex in 400 – 1200 mg of human plasma protein.

• The 2500 U presentation of FEIBA contains 2500 U (units) of anti-inhibitor coagulant complex in 1000 – 3000 mg of human plasma protein.

  • FEIBA also contains factors II, IX, and X, mainly non-activated, as well as activated factor VII. Coagulant factor VIII antigen (F VIII C:Ag), as well as components of the kallikrein-kinin system, are present only in trace amounts.
  • Other components are sodium chloride and sodium citrate.

Solvent

• Water for injections

Appearance of the product and contents of the pack

The product is presented as a lyophilized powder or friable solid, white to off-white or pale green in colour. The reconstituted solution has a pH between 6.8 and 7.6.

The powder and solvent are supplied in glass vials closed with rubber stoppers.

Presentation: 1 x 500 U

1 x 1000 U

1 x 2500 U

Only some pack sizes may be marketed.

[For the leaflet for administration with needles]

Contents of the pack:

• 1 vial with 500 U / 1000 U of FEIBA - powder for solution for infusion
• 1 vial with 10 ml / 20 ml of water for injections
• 1 disposable syringe
• 1 disposable needle
• 1 butterfly needle
• 1 filter needle
• 1 transfer needle
• 1 venting needle

[For the leaflet for administration with BAXJECT II-Hi-Flow]

Contents of the pack:

• 1 vial with 500 U / 1000 U / 2500 U of FEIBA - powder for solution for infusion
• 1 vial with 10 ml / 20 ml / 50 ml of water for injections
• 1 BAXJECT II Hi-Flow reconstitution set
• 1 disposable syringe
• 1 disposable needle
• 1 butterfly needle

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder

Baxalta Innovations GmbH

Industriestrasse, 67

1221 Vienna, Austria

Manufacturer

Takeda Manufacturing Austria AG
Industriestrasse, 67

1221 Vienna, Austria

Local representative of the Marketing Authorisation Holder

Takeda Farmacéutica España S.A.

Calle Albacete, 5, 9th floor

Edificio Los Cubos

28027 Madrid

Spain

Tel: +34 91 790 42 22

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

Austria:

FEIBA 50 E./ml Pulver und Lösungsmittel zur Herstellung einer Infusionslösung

Croatia:

FEIBA 50 U/ml prašak i otapalo za otopinu za infuziju

Cyprus:

FEIBA 50 U/ml κόνις και διαλύτης για διάλυμα προς έγχυση

Czech Republic: FEIBA NF

Denmark:

Feiba

Estonia:

FEIBA

Finland:

Feiba

Germany: FEIBA 500 E, FEIBA 1000 E, FEIBA 2500 E

Greece:

FEIBA 50 U/ml κόνις και διαλύτης για διάλυμα προς έγχυση

Ireland:

FEIBA 50 U/ml powder and solvent for solution for infusion

Latvia: Feiba 50 V/ml pulveris un šķīdinātājs infūzijas šķīduma pagatavošanai

Lithuania: Feiba 50 V/ml milteliai ir tirpiklis infuziniam tirpalui

Malta: FEIBA 50 U/ml powder and solvent for solution for infusion

Netherlands: FEIBA 50 E/ML, poeder en oplosmiddel voor oplossing voor injectie

Norway:

Feiba

Romania:

FEIBA 50 U/ml pulbere si solvent pentru solutie injectabila

Slovakia: FEIBA 50 U/ml prášok a rozpúšťadlo na infúzny roztok

Slovenia:

FEIBA 50 e./ml prašek in vehikel za raztopino za infundiranje

Spain:

FEIBA 50 U/ml polvo y disolvente para solución para perfusión

Sweden:

Feiba 50 enheter/ml pulver och vätska till infusionsvätska, lösning

Date of the most recent revision of this leaflet: August 2024

Detailed and up-to-date information on this medicinal product 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:

Treatment should be initiated and monitored under the supervision of a physician experienced in the treatment of coagulation disorders.

Dosage

The dose and duration of therapy depend on the severity of the hemostatic dysfunction, the location and severity of bleeding, and the patient's clinical condition.

The dose and frequency of administration should always be determined based on clinical efficacy in each individual case.

As a general guideline, doses of 50–100 U/kg of FEIBA are recommended; a single dose exceeding 100 U/kg or a maximum daily dose exceeding 200 U/kg should not be exceeded unless the severity of bleeding requires and justifies higher doses.

Due to patient-specific factors, the response to a bypassing agent may vary, and in a given bleeding situation, patients with an insufficient response to one agent may respond to another. If there is an insufficient response to a bypassing agent, consideration should be given to using an alternative agent.

Paediatric population

Experience in children under 6 years of age is limited; the same dosing regimen as in adults should be adapted according to the child's clinical condition.

1. Spontaneous bleeding

Joint, muscle and soft tissue bleeding

For mild to moderate bleeding, a dose of 50 to 75 U/kg is recommended every 12 hours. Treatment should continue until clear signs of clinical improvement appear, such as reduced pain, decreased swelling, or increased joint mobility.

For severe muscle and soft tissue bleeding, e.g., retroperitoneal hemorrhage, a dose of 100 U/kg every 12 hours is recommended.

Mucous membrane bleeding

A dose of 50 U/kg every 6 hours is recommended, with strict patient monitoring (visual control of bleeding, repeated hematocrit measurements). If bleeding is not controlled, the dose may be increased to 100 U/kg; however, a dose exceeding 200 U/kg should not be exceeded.

Other severe bleeding

In severe bleeding, such as CNS bleeding, a dose of 100 U/kg every 12 hours is recommended. In specific cases, FEIBA may be administered every 6 hours until clear signs of clinical improvement are observed (the maximum daily dose of 200 U/kg must not be exceeded).

2. Surgery

For surgical procedures, an initial dose of 100 U/kg may be administered before surgery, followed by another dose of 50–100 U/kg 6 to 12 hours postoperatively. Postoperative maintenance doses of 50–100 U/kg may be administered every 6–12 hours; the dose, dosing intervals, and duration of peri- and postoperative treatment depend on the type of surgery, the patient's general condition, and clinical efficacy in each individual case (the maximum daily dose of 200 U/kg must not be exceeded).

3. Prophylaxis in patients with haemophilia A and inhibitor
   • Prophylaxis of bleeding in patients with high inhibitor titre and frequent bleeding episodes, after failed immune tolerance induction (ITI) or when ITI is not considered:

A dose of 70 to 100 U/kg on alternate days is recommended. If necessary, the dose may be increased to 100 U/kg daily or gradually reduced.

• Prophylaxis of bleeding in patients with high inhibitor titre during immune tolerance induction (ITI):

FEIBA may be administered in combination with factor VIII at a dosing interval of 50–100 U/kg twice daily, until the factor VIII inhibitor titre has decreased to < 2 U.B.*

*1 Bethesda Unit is defined as the amount of antibody that inhibits 50% of factor VIII activity in plasma incubated (2 hours at 37°C).

4. Use of FEIBA in special patient groups

FEIBA has also been used in combination with a factor VIII concentrate as long-term treatment for complete and permanent eradication of factor VIII inhibitor.

Monitoring

In case of inadequate response to treatment with the product, platelet count should be performed, as a sufficient number of functionally intact platelets is considered necessary for effective treatment with FEIBA.

Due to its complex mechanism of action, there is no direct monitoring of the active substances. Coagulation tests such as whole blood clotting time (WBCT), thromboelastography (TEG, r value), and activated partial thromboplastin time (aPTT) generally show only minor shortening, which does not necessarily correlate with clinical improvement. For these reasons, the usefulness of these assays for monitoring FEIBA therapy is very limited.

Method of administration

FEIBA must be administered slowly by intravenous infusion. The infusion rate must not exceed 2 U/kg per minute.

FEIBA must be reconstituted immediately before administration. The solution should be used immediately (as the preparation contains no preservatives). Do not use solutions that are cloudy or contain deposits. Disposal of unused medication and all materials that have come into contact with it must be carried out in accordance with local regulations.

Therapy monitoring

Single doses exceeding 100 U/kg and daily doses exceeding 200 U/kg must not be exceeded. Patients receiving more than 100 U/kg should be monitored for the development of DIC and/or acute coronary ischemia, and for symptoms of thrombotic or thromboembolic events. High doses of FEIBA should be administered only for the shortest time necessary to control bleeding.

If clinically significant changes in blood pressure or pulse rate, respiratory difficulty, cough, or chest pain occur, the infusion must be stopped immediately, and appropriate diagnostic and therapeutic measures should be taken. Laboratory parameters characteristic of DIC include decreased fibrinogen, decreased platelet count, and/or presence of fibrin or fibrinogen degradation products (FDP). Other parameters indicating DIC are marked prolongation of thrombin time, prothrombin time, or activated partial thromboplastin time (aPTT). In patients with haemophilia and inhibitor or with acquired inhibitors of factors VIII, IX, and/or XI, the aPTT is prolonged due to the underlying disease.

Administration of FEIBA in patients with inhibitor may cause an initial "anamnestic" rise in inhibitor levels. During continued administration of FEIBA, inhibitor levels may decrease over time. Both clinical and published data suggest that the efficacy of FEIBA is not reduced.

Patients with haemophilia and inhibitor or with acquired coagulation factor inhibitors receiving FEIBA treatment may be at increased risk of bleeding while simultaneously having an increased risk of thrombosis.

Laboratory tests and clinical efficacy

In vitro assays used to monitor efficacy, such as aPTT, whole blood clotting time (WBCT), and thromboelastography (TEG), do not necessarily correlate with clinical improvement. Therefore, attempts to normalize these values by increasing the FEIBA dose should not be made and are strongly discouraged due to the potential risk of DIC from overdosing.

Importance of platelet count

In case of inadequate response to FEIBA treatment, platelet count is recommended, as a sufficient number of functionally intact platelets is considered necessary for effective FEIBA treatment.

Treatment of patients with haemophilia B and inhibitor

Experience in patients with haemophilia B and factor IX inhibitor is limited due to the rarity of the disease. Five patients with haemophilia B and inhibitor were treated with FEIBA in clinical trials, either on-demand, prophylactically, or during surgical procedures:

In a prospective, open-label, randomised, parallel-group clinical study in patients with haemophilia A or B with persistently high inhibitor titres (090701, PROOF), 36 patients were randomised to receive either prophylactic or on-demand treatment for 12 months ± 14 days. The 17 patients in the prophylactic group received 85 ± 15 U/kg of FEIBA administered on alternate days, and the 19 patients in the on-demand group received individualised treatment determined by the physician. Two patients with haemophilia B and inhibitor received on-demand treatment, and one patient with haemophilia B received prophylactic treatment.

The median Annual Bleeding Rate (ABR) for all types of bleeding episodes in the prophylactic group (median ABR = 7.9) was lower than in the on-demand group (median ABR = 28.7), representing a 72.5% reduction in median ABR between treatment groups.

In another completed prospective, non-interventional safety surveillance study of perioperative use of FEIBA (PASS-INT-003, SURF), a total of 34 surgical procedures were performed in 23 patients. The majority of patients (18) had congenital haemophilia A with inhibitor, two had haemophilia B with inhibitor, and three had acquired haemophilia A with inhibitor. The duration of FEIBA exposure ranged from 1 to 28 days, with a mean of 9 days and a median of 8 days. The mean cumulative dose was 88,347 U and the median dose was 59,000 U. In patients with haemophilia B and inhibitor, the longest exposure to FEIBA was 21 days, and the maximum dose administered was 7,324 U.

Additionally, 48 patients have been reported in the literature where FEIBA was used for treatment and prevention of bleeding episodes in patients with haemophilia B and factor IX inhibitor (34 patients with haemophilia B and inhibitor received on-demand treatment, six received prophylactic treatment, and eight received treatment for surgical procedures).

There are also isolated reports of FEIBA use in the treatment of patients with acquired inhibitors against factors IX, X, XI, and XIII.

In rare cases, FEIBA has also been used in patients with von Willebrand factor inhibitor.