summary of product characteristics feiba nf

“This leaflet format has been determined by the Ministry of Health and the content thereof has been checked and 

approved.” Date of approval: October 2010. 

SUMMARY OF PRODUCT CHARACTERISTICS 

FEIBA NF 

Factor VIII Inhibitor Bypassing Activity 

Powder for Solution for Injection 

NAME 

FEIBA NF (Factor VIII Inhibitor Bypassing Activity) 

Powder and solvent for the production of a solution for intravenous administration. 

QUALITATIVE AND QUANTITATIVE COMPOSITION 

(a) Powder: each glass vial contains: 

FEIBA NF 500 U* 1000 U* 

Active ingredient: 

Human Plasma Protein with a Factor Eight 

Inhibitor Bypassing Activity of 

200-600 mg 

500 units 

FEIBA NF 500, 100 0 U with BAXIJET ll Hi-Flow Device, 16. 2. 2012, RH 

400-1200 mg 

1000 units 

Other ingredients: 

Sodium Chloride 160 mg 160 mg 

Sodium Citrate dihydrate 80 mg 80 mg 

*) A solution containing 1 U of FEIBA NF shortens the activated partial thromboplastin time (aPTT) of a factor VIII 

inhibitor plasma to 50% of the buffer value (blank). 

FEIBA NF also contains factors II, IX and X mainly in non-activated form as well as activated factor VII; 

factor VIII coagulant antigen (F VIII C:Ag) is present in a concentration of up to 0.1 U/1 U FEIBA NF. The 

factors of the kallikrein-kinin system are present only in trace amounts, if at all. 

(b) Solvent: each glass vial contains 20 ml sterile water for injections. 

PHARMACEUTICAL FORM AND CONTENTS 

Powder and solvent for solution for injection. 

White, off-white or pale green freeze-dried powder or friable solid. The pH value of the reconstituted 

solution is between 6.8 and 7.6. 

FEIBA NF is available in strengths of 500 U and 1000 U, to be dissolved in 20 ml of sterilised water for 

injections. 

The reconstituted product is intended for intravenous administration. 

THERAPEUTIC INDICATIONS 

FEIBA NF is indicated for the control of bleeding episodes in haemophilia A patients with Factor VIII 

inhibitors and also in patients with acquired Factor VIII inhibitors.

POSOLOGY AND METHOD OF ADMINISTRATION 


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Treatment should be initiated and supervised by a physician experienced in the management of 

haemophilia. 

1. Dosage 

The dosage and duration of the therapy depend on the severity of the haemostasis disturbance, the 

location and extent of the bleeding and on the clinical condition of the patient. 

The dosage and frequency of administration should always be guided by the clinical efficacy in the 

individual case. 

As a general guide a dose of 50 to 100 U of FEIBA NF per kg body weight (bw) is recommended, 

however, a single dose of 100 U/kg bw and a maximum daily dose of 200 U/kg bw should not be 

exceeded. 

Coagulation tests such as the whole blood clotting time (WBCT), the thromboelastogram (TEG, r-value), 

and the aPTT usually show only a minor reduction and may not correlate with clinical improvement. 

Consequently, these tests are only of very limited value in monitoring FEIBA NF therapy. 

1.1. Spontaneous Haemorrhage 

Joint, Muscle and Soft Tissue Haemorrhage 

For minor to moderate bleedings a dose of 50-75 U/kg bw is recommended at 12-hour intervals. 

Treatment should be continued until clear signs of clinical improvement appear, such as relief of pain, 

reduction of swelling or flexibility of the joint. 

For major muscle and soft tissue haemorrhage, such as retroperitoneal bleeding, a dose of 100 U/kg 

bw at 12-hour intervals is recommended. 

Mucous Membrane Haemorrhage 

A dose of 50 U/kg bw is recommended to be given every 6 hours with careful monitoring of the patient 

(visible bleeding site, repeated measurements of haematocrit). If the haemorrhage does not stop, the 

dose may be increased to 100 U/kg bw. (Do not exceed the maximum daily dose of 200 U/kg bw.) 

Other Severe Haemorrhages 

Severe haemorrhages, such as CNS bleedings have been effectively treated with doses of 100 U/kg 

bw at 12-hour intervals. In individual cases FEIBA NF may be given at 6-hour intervals until clear 

clinical improvement is achieved. (Do not exceed the maximum daily dose of 200 U/kg bw.) 

1.2. Surgery 

50-100 U/kg bw should be given at intervals of up to 6 hours, a maximum daily dose of 200 U/kg bw 

should not be exceeded. 

2. Administration 

Reconstitute the product as described under RECONSTITUTION OF THE POWDER FOR SOLUTION FOR 

INJECTION WITH THE BAXJECT II HI-FLOW OR RECONSTITUTION OF THE POWDER FOR SOLUTION 

FOR INJECTION WITH TRANSFER NEEDLE, and inject or infuse slowly by the intravenous route only. Do not 

exceed an injection/infusion rate of 2 U/kg bw per minute. 

CONTRAINDICATIONS 

FEIBA NF must not be used in case of hypersensitivity to any one of the ingredients. 

Depending on therapeutic alternatives, the contraindications below are to be considered relative or 

absolute.


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In the following situations FEIBA NF should only be used when no reaction to treatment with other 

appropriate coagulation factor concentrates is to be expected- such as in case of a high inhibitor titre and 

a life-threatening haemorrhage or risk of bleeding e.g. posttraumatic or postoperative. 

Disseminated Intravascular Coagulation (DIC): 

when results of laboratory tests and/or clinical symptoms clearly indicates a liver damage, there is 

an increased risk of developing DIC due to delayed degradation of activated coagulation factors. 

Coronary heart disease, acute thrombosis and/or embolism: in patients with a tentative or definite 

diagnosis of coronary heart disease as well as in patients with acute thrombosis and/or embolism, 

the use of FEIBA should only be used in life-threatening bleeding episodes. 

SPECIAL WARNINGS AND SPECIAL PRECAUTIONS FOR USE 

1. Special Precautions for Use 

As in case with all intravenously administered plasma products (protein preparation), allergic reactions 

may occur. The patients should be informed about possible early signs of intolerance. In rare cases 

allergic reactions such as reactions from nettle rash, hives, fever, urticarial rashes, feeling of chest 

tightness, respiratory distress, wheezing, and fall in blood pressure due to allergic shock, nausea and 

retching as well as other anaphylactoid reactions of varying severity have been observed after 

administration of FEIBA NF. 

If hypersensitivity reactions occur during administration of FEIBA NF, the injection/infusion should be 

stopped. Minor reactions may be controlled by antihistamines. In case of shock, the current medical 

standards for shock treatment are to be observed. 

In patients with a history of hypersensitivity reactions to plasma derivatives the prophylactic 

administration of antihistamines may be indicated. 

Appropriate vaccination should be considered in patients with an inhibitor against a coagulation 

factor. 

As the quantity of sodium in the maximum daily dose may exceed 200 mg, special care should be 

taken with individuals on a low sodium diet. 

Monitoring of Therapy 

Single doses of 100 U/kg bw and daily doses of 200 U/kg bw should not be exceeded. Patients given 

single doses of 100 U/kg bw should be carefully monitored for the development of DIC or symptoms of 

acute coronary ischaemia. High doses of FEIBA NF should be given only for as long as absolutely 

necessary to stop the bleeding. 

Disseminated Intravascular Coagulation (DIC) 

In case of significant clinical changes in blood pressure, pulse rate, respiratory distress, chest pain and 

cough, the infusion should be stopped promptly and appropriate diagnostic and therapeutic measures are 

to be initiated. Laboratory results indicative of DIC are decreased fibrinogen values, decreased platelet 

count, and/or presence of fibrin/fibrinogen degradation products (FDP). Other parameters of DIC include 

significantly prolonged thrombin time, prothrombin time, or aPTT. 

If coagulation parameters are suspicious of DIC, a physician experienced in coagulation therapies should 

be consulted. 

There is insufficient data in children under 6 years of age to recommend the use of FEIBA NF. However, 

inhibitor formation is a common occurrence in haemophilic children undergoing factor VIII replacement 

therapy. Case studies have shown the successful use of FEIBA NF in the young age group. 

FEIBA NF 500 U and FEIBA NF 1000 U contain approx. 80 mg sodium (calculated) per vial. This has to 

be attended for patients on low sodium diet.


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Acquired haemophilia 

Patients with inhibitor haemophilia or with acquired inhibitors to coagulation factors, who are treated with 

FEIBA NF, may have increased bleeding tendency as well as increased risk of thrombosis at the same 

time. 

Laboratory Tests and Clinical Efficacy 

In vitro tests to control efficacy such as aPTT, whole blood clotting time (WBCT), and thromboelastogram 

(TEG) may not correlate with clinical improvement. For this reason, attempts to normalise these values by 

increasing the dose of FEIBA NF may not be successful and are strongly discouraged because of the 

potential hazard of inducing DIC by overdosage. 

Significance of Platelet Count 

In case of inadequate response to treatment with FEIBA NF it is recommended to perform a platelet 

count, since a sufficient number of functionally intact platelets are considered necessary for the efficacy 

of FEIBA NF. 

Special Warnings 

FEIBA NF is made from human plasma. When medicinal products prepared from human blood or plasma 

are administered, infectious diseases due to transmission of infective agents cannot be totally excluded. 

This also applies to pathogens of hitherto unknown nature. 

The risk of transmission of infective agents is reduced by the following measures: 

-Selection of donors and donations is performed through strict anamnesis, testing of individual 

donations and the plasma pools for HBs antigen and antibodies to HIV and HCV (this indicates 

whether an infection with viruses causing hepatitis B, AIDS or hepatitis C is present). 

-Testing of plasma pools for genomic virus material of HCV. 

-Plasma pools are tested and viral removal/inactivation procedures are included in the production 

process. The following measures have been implemented: Plasma pool testing for virus genome 

sequences of HIV-1 and –2, HBV, HAV (a virus causing hepatitis A), and HCV with the polymerase 

chain reaction (HIQ-PCR 1 ), Non-Returning Donor-Applicant Exclusion, Inventory Hold and the 

Lookback Programme. 

These measures taken are considered effective for enveloped viruses such as human immunodeficiency 

virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV), and for the non-enveloped virus hepatitis 

A virus (HAV) and Parvovirus B19. 

When a pharmaceutical prepared from human plasma is administered regularly / repeatedly, appropriate 

vaccination (hepatitis A and B) is recommended. 

It is advised, for the patient’s benefit, to record the name and batch number of the preparation for each 

administration of FEIBA NF. 

INTERACTION WITH OTHER MEDICINAL PRODUCTS AND OTHER FORMS OF 

INTERACTION 

It is not recommended to use antifibrinolytics such as epsilon-aminocaproic acid in combination with 

FEIBA NF. 

If treatment with both antifibrinolytics such as epsilon-aminocaproic acid and FEIBA NF is indicated, the 

products should be administered at least 6 hours apart. 

1 

HIQ-PCR is a quality-assured PCR testing programme for genome equivalents of HIV-1 and –2, HBV, and HCV. 

HIQ-PCR stands for Hyland Immuno Quality-Assured Polymerase Chain Reaction.

PREGNANCY AND LACTATION 


5 

Animal reproduction studies have not been conducted with FEIBA NF based on the rare occurrence of 

haemophilia in women. Experience regarding the use of FEIBA NF during pregnancy and breast feeding 

is not available. Therefore, due to the increased risk of thrombosis during pregnancy, FEIBA NF should 

only be used under careful medical monitoring and if no alternative therapy is available. 

EFFECTS ON ABILITY TO DRIVE AND USE MACHINES 

No effects of FEIBA NF on the ability to drive and operate machinery have been observed. 

SIDE EFFECTS 

Rapid intravenous injection or infusion may cause stabbing pain and numbness in the face and 

extremities as well as a drop in blood pressure. 

Following adverse reactions have been reported during post marketing. The frequency cannot be 

estimated due to the nature of the data and therefore is categorized as unknown: 

System organ classes according to 

MedDRA 

Preferred MedDRA term 

Blood and lymphatic system disorders Disseminated intravascular coagulation (DIC) 

Cardiac disorders Myocardial infarction 

General disorders and administration site 

conditions (Disorders during injection) 

Injection site pain 

Immune system disorders Hypersensitivity 

Urticaria 

Anaphylactic reaction 

Investigations Blood pressure decreased 

Nervous system disorders Hypoaesthesia 

Skin and subcutaneous tissue disorders Hypoaesthesia facial 

Vascular disorders Embolism 

Myocardial infarctions occurred after the administration of doses above the maximum daily dose and/or 

prolonged application and/or the presence of risk factors for thromboembolism. 

OVERDOSAGE 

Overdosage of FEIBA NF may increase the risk of side effects such as thromboembolism, DIC or 

myocardial infarction (see section "Special Precautions for Use"). 

PHARMACOLOGICAL PROPERTIES 

Pharmacotherapeutic group: Activated prothrombin complex against factor VIII antibody, 

ATC Code: B02BD03 

Pharmacodynamic properties 

Although FEIBA was developed in the early 1970s and its factor VIII inhibitor bypassing activity has been 

demonstrated both in vitro and in vivo, its active principle is still the subject of scientific debate. However, 

recent scientific work indicates a role of specific components of the activated prothrombin complex, 

zymogen prothrombin (F II) and activated Factor X (FXa), in the FEIBA NF mode of action.

Pharmacokinetic properties 


6 

Since the mode of action of FEIBA NF is still being discussed, it is not possible to make a final statement 

to the pharmacokinetic properties. 

Preclinical Safety data 

Based on acute toxicity studies with factor VIII knockout mice and normal mice and rats with higher doses 

than the maximum daily dose for humans (> 200 U/kg of body weight), it can be concluded that the side 

effects in connection with FEIBA NF mainly result from hypercoagulation due to the pharmacological 

properties. 

Toxicity studies with repeated administration are unpractical in animal experiments, since the 

development of antibodies against heterologous proteins causes interference. 

Since human blood-clotting factors are not considered carcinogenic or mutagenic, studies with animal 

experiments, especially for heterologous species were regarded as unnecessary. 

INCOMPATIBILITIES 

As for any blood coagulation factor concentrate, FEIBA NF should not be mixed with other medicinal 

products before administration as this might impair the efficacy and safety of the product. It is advisable to 

rinse a common venous access with isotonic sodium chloride solution prior to and after infusion of 

FEIBA NF. 

SHELF LIFE 

The freeze-dried product has a shelf life of two years. 

Chemical and physical stability of the reconstituted product has been demonstrated for 3 hours at a 

temperature of 20�C –25�C. 

Considering microbiological aspects, FEIBA NF should be used immediately after reconstitution. If the 

ready-made solution is not used immediately, the user will be responsible for the conditions and time of 

storage. 

The ready to use solution must not be refridged. 

SPECIAL PRECAUTIONS FOR STORAGE 

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

Store in the original package, to protect the contents from light. 

Store out of the reach of children.

NATURE AND CONTENTS OF THE CONTAINER 


7 

Powder and solvent come in glass vials made of surface-treated, colourless glass (hydrolytic class II). 

The product vial is closed with a chlorobutyl rubber stopper, while the solvent vial is closed with a 

bromobutyl rubber stopper. 

Each package contains either : 

- 1 rubber-capped vial of FEIBA NF 500 or 1000 U (powder for reconstituting solution for 

intravenous administration). 

- 1 rubber-capped vial containing 20 ml sterile water for injections. 

- 1 disposable syringe (20 ml capacity). 

- 1 disposable needle. 

- 1 butterfly needle with clamp (winged set for injection).. 

- 1 filter needle. 

- 1 transfer needle. 

- 1 aeration needle. 

or 

1 rubber-capped vial with FEIBA NF – powder for solution for intravenous 

administration 

1 rubber-capped vial with 20 ml sterilised Water for Injections 

1 Baxject II Hi-Flow – Needleless transfer device intended for transferring and mixing drugs contained in 

two vials into a syringe 

1 disposable syringe 

1 disposable needle 

1 butterfly needle with clamp (winged set for injection) 

SPECIAL PRECAUTIONS FOR DISPOSAL AND OTHER HANDLING ADVICE 

To prepare the FEIBA NF solution, use only the sterilised water for injections and the reconstitution 

device provided in the pack. Use aseptic technique throughout entire procedure. FEIBA NF is to be 

reconstituted only immediately before administration. The solution should then be used straight away (the 

solution does not contain preservatives). Do not use solutions which are cloudy or have deposits. Do not 

use if the needleless transfer device or the transfer needle, its sterile barrier system or its packaging is 

damaged or shows any sign of deterioration. 

Any unused medicinal product or waste material is to be disposed of in accordance with national 

requirements. 

RECONSTITUTION OF THE POWDER FOR SOLUTION FOR INJECTION WITH THE BAXJECT II HI- 

FLOW: 

1. Warm solvent (sterilised water for injections) vial to room temperature (15 �C – 25 �C), for 

example by using a water bath for several minutes (max. 37°C). 

2. Remove the protective caps from the FEIBA NF vial and solvent vial and cleanse the rubber 

stoppers of both. Place the vials on a flat surface. 

3. Open the BAXJECT II Hi-Flow device package by peeling away the paper lid without touching the 

inside (Fig a). Do not remove the device from the package. 

4. Turn the package over and insert the clear plastic spike through the solvent stopper (Fig. b). Grip 

the package at its edge and pull the package off BAXJECT II Hi-Flow (Fig. c). Do not remove the 

blue cap from BAXJECT II Hi-Flow device. 

5. With BAXJECT II Hi-Flow attached to the solvent vial, invert the system so that the solvent vial is 

on top of the device. Insert the purple plastic spike through the FEIBA vial stopper. The vacuum 

will draw the solvent into the FEIBA NF vial (Fig. d) 

6. Swirl gently until all material is dissolved. Ensure that FEIBA NF is completely dissolved, 

otherwise active material will not pass through the device filter.

Figure a Figure b Figure c 

8 

Instructions for Injection/Infusion: 

1. Remove the blue cap from BAXJECT II Hi-Flow. Take the syringe and connect it to BAXJECT II 

Hi-Flow (DO NOT DRAW AIR INTO THE SYRINGE) (Fig. e). 

2. Invert the system (with FEIBA NF vial on top). Draw the FEIBA NF solution into the syringe by 

pulling the plunger back slowly (Fig. f) 

3. Disconnect the syringe. 

4. Slowly inject the solution intravenously with a winged set for injection (or a disposable needle) 

Figure d Figure e Figure f 

Do not exceed an injection speed of 2 U FEIBA/kg body weight per minute. 

RECONSTITUTION OF THE POWDER TO PREPARE A SOLUTION FOR INJECTION WITH 

TRANSFER NEEDLE: 

1. Warm the unopened vial containing the solvent (sterile water for injections) to room temperature, e.g. 

using a sterile water bath for warming within several minutes (max. +37°C). 

2. Remove protective caps from the concentrate vial and solvent vial (fig. 1) and disinfect the rubber 

stoppers of both 2 vials. 

3. Remove protective covering from one end of the supplied "transfer needle" by twisting and pulling 

(fig. 2). Insert the exposed needle through the rubber stopper of the solvent vial (fig. 3). 

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

exposed end. 

5. Invert the solvent vial over the concentrate vial, and insert the free end of the transfer needle through 

the rubber stopper of the concentrate vial (fig. 4). The solvent will be drawn into the concentrate vial 

by vacuum. 

FEIBA NF 500, 100 0 U with BAXIJET ll Hi-Flow Device, 16. 2. 2012, RH


9 

6. Disconnect the two vials by removing the needle from the concentrate vial (fig. 5). 

Gently agitate or rotate the concentrate vial to accelerate dissolution. 

7. Upon complete reconstitution of the concentrate, insert the enclosed "aeration needle" provided 

(fig. 6) and any foam will collapse. Remove aeration needle. 

INJECTION/INFUSION: 

1. Remove protective covering from the supplied "filter needle" by twisting and pulling and fit the needle 

onto a sterile disposable syringe. Draw the solution into the syringe (fig. 7). 

2. Disconnect the filter needle from the syringe and slowly inject the solution intravenously by means of 

the enclosed infusion set (and disposable needle, respectively). 

If administered by infusion, a disposable infusion set with adequate filter is to be used. 

Do not exceed an injection/infusion rate of 2 units FEIBA NF per kg of body weight per minute. 

If devices other than those supplied with FEIBA NF are used, ensure use of an adequate filter with at 

least 149 µm pore size. 

After injection/infusion: put all needles together with the syringe and/or the venepuncture instruments into 

the product box without closing them to avoid endangering other persons. 

The administration of the preparation must be documented by means of the attached adhesive labels in 

the anamnesis. 

REGISTRATION NUMBERS: 

FEIBA NF 500 Units: 026 14 25389 00 

FEIBA NF 1000 Units: 026 15 25390 00 

MANUFACTURER 

Baxter AG 

Industriestrasse 67 

A-1220 Vienna, Austria. 

LICENCE HOLDER 

Teva Medical (Marketing) Ltd 

P.O.Box 2, Ashdod 77100 

fig. 1 fig. 2 fig. 3 fig. 4 fig. 5 fig. 6 fig. 7

summary of product characteristics feiba nf

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