Treatment of bleeding in hemophilia A patients with inhibitors.                                                                                                                                                                                   Treatment of bleeding in hemophilia B patients with inhibitors, if no other specific treatment is available (see section 5.1).
Treatment of bleeding in non-hemophiliacs with acquired inhibitors to factor VIII.
Prophylaxis of bleeding in hemophilia A patients with inhibitors who have experienced a significant bleed or are at high risk of significant bleeding.

The treatment is to be initiated and monitored by a physician experienced in the treatment of coagulation disorders.

Posology
Dosage and duration of treatment depend on the severity of the haemostatic disorder, the localization and the extent of the bleeding, as well as the clinical condition of the patient.
Dosage and frequency of administration should always be guided by the clinical efficacy in each individual case.
As a general guideline, a dose of 25 –100 U FEIBA per kg body weight is recommended; a single dose of 100 U/kg body weight and a maximum daily dose of 200 U/kg body weight must not be exceeded unless the severity of bleeding warrants and justifies the use of higher doses.
See section 4.4.

Paediatric use (children)
The experience in children under 6 years of age is limited; the same dose regimen as in adults should be adapted to the child’s clinical condition.

1)    Spontaneous bleeding
Joint, muscle and soft tissue hemorrhage
A dose of 25 – 75 U/kg body weight at 12-hour intervals is recommended for minor to moderately severe bleeding. The treatment is to be continued until a clear improvement of the clinical symptoms, e.g. reduction of pain, decrease of swelling or increase of joint mobility, occurs.
For severe muscle and soft tissue bleeding, e.g. retroperitoneal hemorrhages, a dose of 100 U/kg body weight at 12-hour intervals is recommended.                                                           Mucous membrane hemorrhage
A dose of 25 U/kg body weight every 6 hours under careful monitoring of the patient (visual control of bleeding, repeated determination of hematocrit) is recommended. If the bleeding does not stop, the dose may be increased to 100 U/kg body weight, however a daily dose of 200 U/kg body weight must not be exceeded.

Other severe hemorrhages                                                                                                                                                                                                                                                                                                                 In severe hemorrhage, such as CNS bleeding, a dose of 100 U/kg body weight at 12-hour intervals is recommended. In individual cases, FEIBA may be administered at 6-hour intervals, until clear improvement of the clinical condition is achieved. (The maximum daily dose of 200 U/kg body weight must not be exceeded!)

2)    Surgery
In surgical interventions, an initial dose of 100 U/kg body weight may be administered preoperatively, and a further dose of 25 – 100 U/kg body weight may be administered after 6 – 12 hours. As a postoperative maintenance dose, 25 – 100 U/kg body weight may be administered at 6 – 12-hour intervals; dosage, dosage intervals and duration of the peri- and postoperative therapy are guided by the surgical intervention, the patient’s general condition and the clinical efficacy in each individual case. (The maximum daily dose of 200 U/kg body weight must not be exceeded!)

3)    Prophylaxis in hemophilia A patients with inhibitors
Prophylaxis of bleeding in patients with a high inhibitor titer and frequent hemorrhages after failed immune tolerance induction (ITI) or when an ITI is not considered:
a dose of 70 – 100 U/kg body weight every other day is recommended. If necessary, the dose may be increased to 100 U/kg body weight per day or it may be decreased gradually.

Prophylaxis of bleeding in patients with a high inhibitor titer during an immune tolerance induction (ITI):
FEIBA may be administered concomitantly with factor VIII administration, in a dosage range of 25 – 100 U/kg body weight, twice per day, until the factor VIII inhibitor titer has decreased to < 2 B.U.*
1 Bethesda Unit is defined as the amount of antibodies which inhibits 25% factor VIII activity in incubated plasma (2 h at 37°C).

4)    Use of FEIBA in special patient groups
See Section 5.1 for information in relation to hemophilia B patients with factor IX inhibitor.
In combination with factor VIII concentrate, FEIBA was also used for long term therapy to achieve complete and permanent elimination of the factor VIII inhibitor.

Monitoring
In case of inadequate response to treatment with the product, it is recommended that a platelet count be performed because a sufficient number of functionally intact platelets are considered to be necessary for the efficacy of the product.
Due to the complex mechanism of action, no direct monitoring of active ingredients is available. Coagulation tests such as the whole blood coagulation time (WBCT), the thromboelastogram (TEG, r-value) and the aPTT usually show only little reduction and do not necessarily correlate with the clinical efficacy. Therefore these tests have little significance in the monitoring of the therapy with FEIBA. See section 4.4.

Method of administration
Reconstitute the product as described in section 6.6 and slow infusion via the intravenous route. An infusion rate of 2 U/kg body weight per minute must not be exceeded.

WARNINGS
Hypersensitivity Reactions
FEIBA can precipitate allergic-type hypersensitivity reactions that have included, urticaria, angioedema, gastrointestinal manifestations, bronchospasm, and hypotension; these reactions can be severe and can be systemic (e.g., anaphylaxis with urticaria and angioedema, bronchospasm, and circulatory shock). Other infusion reactions, such as chills, pyrexia, and hypertension have also been reported.
Patients should be informed of the early signs of hypersensitivity reactions, for example erythema, skin rash, generalized urticaria, pruritus, breathing difficulties/dyspnoea, tightness of the chest, general indisposition, dizziness and drop in blood pressure up to allergic shock.
At the first sign or symptom of an infusion/hypersensitivity reaction, FEIBA administration should be stopped and medical care initiated as appropriate.
When considering re-exposure to FEIBA in patients with suspected hypersensitivity to the product or any of its components, the expected benefit and the risk of re-exposure must be carefully weighed, taking into account the known or suspected type of the patient’s hypersensitivity (allergic or non-allergic), including potential remedial and/or preventative therapy or alternative therapeutic agents.

Thrombotic and Thromboembolic Events
Thrombotic and thromboembolic events, including disseminated intravascular coagulation (DIC), venous thrombosis, pulmonary embolism, myocardial infarction, and stroke, have occurred in the course of treatment with FEIBA.

Some of these events occurred with doses above 200 U/kg/day or in patients with other risk factors (including DIC, advanced atherosclerotic disease, crush injury or septicemia) for thromboembolic events. Concomitant treatment with recombinant Factor VIIa likely increases the risk of developing a thromboembolic event. The risk of thrombotic and thromboembolic events may be increased with high doses of FEIBA.
The possible presence of such risk factors should always be considered in patients with congenital and acquired hemophilia.

FEIBA should be used with particular caution and only if there are no therapeutic alternatives in patients with an increased risk of thromboembolic complications. These include, but are not limited to, patients with a history of coronary heart disease, liver disease, DIC, arterial or venous thrombosis, post-operative immobilization, elderly patients and neonates.
Thrombotic microangiopathy (TMA) has not been reported in FEIBA clinical studies. Cases of TMAs were reported in an emicizumab clinical trial where subjects received FEIBA as part of a treatment regimen for breakthrough bleeding (clinical discussion in the European Public Assessment Report (EPAR) of emicizumab; see also Oldenburg et al. Emicizumab Prophylaxis in Hemophilia A with Inhibitors. N Engl J Med 2017:377:809-818).
The safety and efficacy of FEIBA for breakthrough bleeding in patients receiving emicizumab has not been established.
Therefore, benefit-risk evaluation of FEIBA to be administered to emicizumab exposed patients is required, and patients must be closely monitored by their physicians. (see also section 4.5.)                                                             If signs or symptoms of thrombotic and thromboembolic events are observed, the infusion should be stopped immediately and appropriate diagnostic and therapeutic measures initiated. A single dose of 100 U/kg body weight and a daily dose of 200 U/kg body weight should not be exceeded unless the severity of bleeding warrants and justifies the use of higher doses.
When used to stop bleeding, the product should be given only for as long as absolutely necessary to achieve the therapeutic goal.

Therapy monitoring
Individual doses of 100 U/kg body weight and daily doses of 200 U/kg body weight must not be exceeded. Patients receiving 100 U/kg body weight or more must be monitored carefully, particularly for the development of DIC and/or acute coronary ischemia and for symptoms of other thrombotic or thromboembolic events. High doses of FEIBA should be administered only as long as strictly necessary – in order to stop a hemorrhage.
If clinically significant changes in blood pressure or pulse rate, respiratory distress, coughing or chest pain occur, the infusion is to be discontinued immediately and appropriate diagnostic and therapeutic measures are to be initiated. Significant laboratory parameters for DIC are a drop in fibrinogen, a drop of the thrombocyte count and/or the presence of fibrin/fibrinogen degradation products (FDP). Other parameters for DIC are a clearly prolonged thrombin time, prothrombin time or aPTT. In patients with inhibitor hemophilia or with acquired inhibitors to factors VIII, IX and/or XI, the aPTT is prolonged by the underlying disease.
Patients with inhibitor hemophilia or with acquired inhibitors to coagulation factors, who are treated with FEIBA, may have increased bleeding tendency as well as increased risk of thrombosis at the same time.

Laboratory tests and clinical efficacy
In vitro tests, such as aPTT, whole blood coagulation time (WBCT) and thromboelastograms (TEG) as proof of efficacy do not have to correlate with the clinical picture. Therefore, attempts to normalize these values by increasing the dose of FEIBA cannot be successful, and are even to be strongly rejected because of the possible risk of triggering a DIC through overdosing.

Significance of the thrombocyte count
If the response to treatment with FEIBA is inadequate, conducting a thrombocyte count is recommended since a sufficient number of functionally intact thrombocytes is necessary for the efficacy of FEIBA.

PRECAUTIONS
Thrombotic and Thromboembolic Complications
In the following situations, FEIBA is to be applied only if no reaction to treatment with suitable blood coagulation factor concentrates can be expected – e.g. in case of a high inhibitor titer and a life-threatening hemorrhage or risk of bleeding (e.g. post-traumatically or postoperatively):
-    Disseminated intravascular coagulation (DIC): laboratory findings and/or clinical symptoms                                                                                                                                                                                                                                                                                                                                                           -    Liver damage: Due to the delayed clearance of activated coagulation factors, patients with impaired liver function are at increased risk of developing DIC.
-    Coronary heart disease, acute thrombosis and/or embolism.

Patients who receive FEIBA should be monitored for the development of DIC, acute coronary ischemia, and signs and symptoms of other thrombotic or thromboembolic events. At the first signs or symptoms of thrombotic and thromboembolic events, the infusion should be stopped immediately and appropriate diagnostic and therapeutic measures initiated.

Discordant Response to Bypassing Agents
Due to patient-specific factors the response to a bypassing agent can vary, and in a given bleeding situation patients experiencing insufficient response to one agent may respond to another agent. In case of insufficient response to one bypassing agent, use of another agent should be considered.

Anamnestic Responses
Administration of FEIBA to patients with inhibitors may result in an initial “anamnestic” rise in inhibitor levels. Upon continued administration of FEIBA, inhibitors may decrease over time.
Clinical and published data suggest that the efficacy of FEIBA is not reduced.

Interference with Laboratory Tests
After administration of high doses of FEIBA, the transitory rise of passively transferred Hepatitis B surface antibodies may result in misleading interpretation of positive results in serological testing.
FEIBA contains blood group isohemagglutinins (anti-A and anti-B). Passive transmission of antibodies to erythrocyte antigens, e.g., A, B, D, may interfere with some serological tests for red cell antibodies, such as antiglobulin test (Coombs test).

Pediatrics
Case reports and limited clinical trial data suggest that FEIBA can be used in children younger than 6 years of age. The same dose regimen as in adults should be adapted to the child’s clinical condition.

Elderly
There are only limited clinical trial data with the use of FEIBA in elderly patients.

Prophylactic use in hemophilia B patients with inhibitors
Due to the rarity of the disease, only limited clinical data is available for the prophylaxis of bleeding in hemophilia B patients (literature case reports, n = 4, and clinical data in prophylaxis study 090701, n = 1).

Transmission of infectious agents
Standard measures to prevent infections resulting from the use of medicinal products prepared from human blood or plasma include selection of donors, screening of individual donations and plasma pools for specific markers of infection and the inclusion of effective manufacturing steps for the inactivation / removal of viruses. Despite this, when medicinal products prepared from human blood or plasma are administered, the possibility of transmitting infective agents cannot be totally excluded. This also applies to unknown or emerging viruses and other pathogens.
The measures taken are considered effective for enveloped viruses such as HIV, HBV and HCV, and for the non-enveloped virus HAV. The measures taken may be of limited value against non-enveloped viruses such as parvovirus B19. Parvovirus B19 infection may be serious for pregnant women (fetal infection) and for individuals with immunodeficiency or increased erythropoiesis (e.g. haemolytic anaemia).

It is strongly recommended that every time that FEIBA is administered to the patient, the name and batch number of the product are recorded in order to maintain a link between the patient and the batch of the product.
Appropriate vaccination (hepatitis A and B) should be considered for patients in regular/ repeated receipt of human plasma-derived products including FEIBA.

Excipient related considerations
FEIBA 25 U/ml contains approximately 2 mg sodium (calculated) per ml; it is approx. 20 mg sodium for the presentation 500 U FEIBA, approx. 40 mg sodium for the presentation 1000 U FEIBA and approx. 200 mg sodium for the presentation 2500 U FEIBA. This is to be taken into consideration in patients on a low sodium diet.

No adequate and well-controlled studies of the combined or sequential use of FEIBA NF and recombinant Factor VIIa, antifibrinolytics or emicizumab have been conducted. The possibility of thromboembolic events should be considered when systemic antifibrinolytics such as tranexamic acid and aminocaproic acid are used during treatment with FEIBA. Therefore, antifibrinolytics should not be used for approximately 6 to 12 hours after the administration of FEIBA.
In cases of concomitant rFVIIa use a potential drug interaction cannot be excluded according to available in vitro data and clinical observations (potentially resulting in adverse events such as a thromboembolic event).
Clinical experience from an emicizumab clinical trial suggests that a potential drug interaction may exist with emicizumab when FEIBA was used as part of a treatment regimen for breakthrough bleeding which may result in thromboembolic events and thrombotic microangiopathy (see section 4.4).

There are no adequate data from the use of FEIBA in pregnant or lactating women. Physicians should balance the potential risks and only prescribe FEIBA if clearly needed, taking into consideration that pregnancy and the postpartum period confer an increased risk of thromboembolic events, and several complications of pregnancy that are associated with an increased risk of DIC.
No animal reproduction studies have been conducted with FEIBA, and the effects of FEIBA on fertility have not been established in controlled clinical trials.
See section 4.4 for information on parvovirus B19 infection.

FEIBA has no, or negligible, influence on the ability to drive or to use machines.

FEIBA can precipitate allergic-type hypersensitivity reactions that have included urticaria, angioedema, gastrointestinal manifestations, bronchospasm, and a drop in blood pressure; these reactions can be severe and can be systemic (e.g., anaphylaxis with urticaria and angioedema, bronchospasm, and circulatory shock). See also section 4.4 Hypersensitivity Reactions.

The adverse reactions presented in this section have been reported from post marketing surveillance as well as from 2 studies with FEIBA for the treatment of bleeding episodes in pediatric and adult patients with hemophilia A or B and inhibitors to factors VIII or IX. One study also enrolled acquired hemophilia patients with factor VIII inhibitors (2 of 49 patients). The adverse reactions from a third study comparing prophylaxis with on-demand treatment have been added.
 
Frequency categories are defined according to the following convention: very common    ≥ 1/10
common    ≥ 1/100 to <1/10 uncommon    ≥ 1/1,000 to <1/100 rare    ≥ 1/10,000 to <1/1,000
very rare    < 1/10,000
unknown    cannot be estimated from the available data                                                                                                                                                                                                                                                                                                                                                    Class Reactions
Other symptoms of hypersensitivity reactions to plasma-derived products include lethargy and restlessness.

Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of FEIBA is important. It allows continued monitoring of the benefit/risk balance of FEIBA. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system:

To report any side effect(s):
Kingdom of Saudi Arabia
-National Pharmacovigilance centre (NPC)
•    Fax: +966-11-205-7662
•    Call NPC at +966-11-2038222, Ext: 2317-2356-2340
•    Reporting hotline: 19999
•    E-mail: npc.drug@sfda.gov.sa
•    Website: www.sfda.gov.sa/npc

•    Other GCC States:
- Please contact the relevant competent authority.

The risk of thrombotic and thromboembolic events (including DIC, myocardial infarction, venous thrombosis, and pulmonary embolism) may be increased with high doses of FEIBA. Some of the reported thromboembolic events occurred with doses above 200 U/kg or with patients with other risk factors for thromboembolic events. If signs or symptoms of thrombotic and thromboembolic events are observed, the infusion should be stopped immediately and appropriate diagnostic and therapeutic measures initiated. See section 4.4.

Pharmacotherapeutic group: blood coagulation factors, ATC code: B02BD03.

Although FEIBA was developed in the early seventies and its factor VIII inhibitor bypassing activity has been proven in vitro as well as in vivo, its mode of action is still the subject of scientific discussion. FEIBA, as found with activity assays, is composed of prothrombin complex zymogens which are both procoagulant (prothrombin FVII, FIX, FX) and anticoagulant (protein C) in relatively equal quantities to the arbitrary FEIBA potency unit but its procoagulant enzyme content is relatively low. FEIBA, thus, contains the proenzymes of the prothrombin complex factors, but only very small amounts of their activation products, with the contents of FVIIa being the highest. [Turecek PL and Schwarz HP. Chapter 4: Factor Eight Inhibitor Bypassing Activity, in Production of Plasma Proteins for Therapeutic Use, eds.
Joseph Bertolini, Neil Goss, John Curling, Wiley 2013, ISBN: 978-0-470-92431-0].

Current scientific works point to the role of specific components of the activated prothrombin complex, prothrombin (F II) and activated factor X (FXa) in the mode of action of FEIBA. [Turecek PL, Varadi K, Gritsch H, et al. Factor Xa and Prothrombin: Mechanism of Action of FEIBA. Vox Sang. 77: 72-79, 1999]
FEIBA controls bleeding by induction and facilitation of thrombin generation, a process for which the formation of the prothrombinase-complex is crucial. A number of biochemical in vitro and in vivo studies have shown that FXa and prothrombin play a critical role in the activity of FEIBA. The prothrombinase complex has been found to be a major target site for FEIBA. Apart from prothrombin and FXa, FEIBA contains other proteins of the prothrombin complex, which could also facilitate haemostasis in haemophilia patients with inhibitors.

Treatment of hemophilia B patients with inhibitors
The experience in hemophilia B patients with factor IX inhibitors is limited due to the rarity of the disease. Five hemophilia B patients with inhibitors were treated with FEIBA during clinical trials either on-demand, prophylactically or for surgical interventions:

In a prospective open-label, randomized, parallel clinical study in hemophilia A or B patients with persistent high-titer inhibitors (090701, PROOF), 36 patients were randomized to either 12 months ± 14 days of prophylactic or on-demand therapy. The 17 patients in the prophylaxis arm received 85 ± 15 U/kg FEIBA administered every other day and the 19 patients in the on- demand arm were treated individually determined by the physician. Two hemophilia B patients with inhibitors were treated in the on-demand arm and one hemophilia B patient was treated in the prophylactic arm.
The median ABR (annualized bleeding rate) for all types of bleeding episodes in patients in the prophylaxis arm (median ABR = 7.9) was less than that of patients in the on-demand arm (median ABR = 28.7), which amounts to a 72.5% reduction in median ABRs between treatment arms.

In another completed prospective non-interventional surveillance study of the perioperative use of FEIBA (PASS-INT-003, SURF) a total of 34 surgical procedures were performed in 23 patients. The majority of patients (18) were congenital hemophilia A patients with inhibitors, two were hemophilia B patients with inhibitors and three were patients with acquired hemophilia A with inhibitors. 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. For hemophilia B patients with inhibitors, the longest exposure to FEIBA was 21 days and the maximum dose applied was 7324 U.
In addition 36 case reports are available when FEIBA was used for treatment and prevention of bleeding episodes in hemophilia B patients with factor IX inhibitor (24 hemophilia B patients with inhibitors were treated on-demand, four hemophilia B patients with inhibitors were treated prophylactically and eight hemophilia B patients with inhibitors were treated for surgical procedures).

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

As the mode of action of FEIBA is still being discussed, it is not possible to make a conclusive statement about the pharmacokinetic properties.

Based on acute toxicity studies in factor VIII knockout mice and in normal mice, and in rats, with doses higher than the maximum daily dose in humans (> 200 U/kg body weight), it can be concluded that the side effects in connection with FEIBA are mainly the result of hypercoagulation due to the pharmacological properties.

Toxicity studies with repeated administration in animal experiments are practically unfeasible as interference occurs through the development of antibodies to heterologous proteins.

Since human blood coagulation factors are not seen as carcinogenic or mutagenic, experimental animal studies, especially in heterologous species, were not considered necessary.

Powder:    Sodium chloride Sodium citrate

Solvent:    Water for Injections

This medicinal product must not be mixed with other medicinal products except the solvent mentioned in section 6.6.
As in all blood coagulation preparations, the efficacy and tolerance of the medicinal product may be impaired by being mixed with other medicinal products. It is advisable to rinse a common venous access with a suitable solution, e.g. with isotonic saline solution, before and after the administration of FEIBA.
Coagulation factors derived from human plasma may be adsorbed by the inner surfaces of certain types of injection/infusion devices. If this were to occur, it could result in failure of therapy. Therefore, only approved plastic infusion devices may be used with FEIBA.

Do not store above 25°C. Do not freeze.
Store in the original package in order to protect from light. For storage conditions of the reconstituted medicinal product – see section 6.3.

The powder is supplied in a vial made of surface treated, colorless glass (hydrolytic type I for 500 U). The solvent is supplied in a vial made of surface treated, colorless glass (hydrolytic type I for  20 ml. The vials are closed by a stopper made of butyl rubber.
FEIBA 25 U/ml is available in the following presentations: 1 x 500 U                                                                                                                                                                            Presentation 500 U contains:

-    1 vial with 500 U FEIBA powder for solution for infusion
-    1 vial with  20 ml Water for Injections
-    1 disposable syringe
-    1 disposable needle
-    1 butterfly needle with clamp
-    1 filter needle
-    1 transfer needle
-    1 aeration needle
or
-    1 vial with 500 U FEIBA powder for solution for infusion
-    1 vial with 20 ml Water for Injections
-    1 BAXJECT II Hi-Flow
-    1 disposable syringe
-    1 disposable needle
-    1 butterfly needle with clamp

Not all presentations or package variants may be marketed.

FEIBA is to be reconstituted immediately prior to administration. The solution should be used immediately (as the preparation does not contain preservatives).

Swirl gently until all material is dissolved. Ensure that FEIBA is completely dissolved; otherwise, less FEIBA Units will pass through the device filter.

After reconstitution, the solution should be inspected for particulate matter and discoloration prior to administration. Do not use solutions which are cloudy or have deposits.

Open containers must not be re-used.

Do not use the product if its sterile barrier has been breached, its package damaged or if it shows signs of deterioration.                                                                                                                                                                                                                        Use only the included Water for Injections and the included device set for reconstitution. If devices other than those enclosed are used, ensure the use of an adequate filter with a pore size of at least 149 µm.

Any unused product or waste material should be disposed of in accordance with local requirements.                                                                                                                                                                                                                                                                                                                                                         Reconstitution of the powder for preparing a solution for infusion with needles:
1.    Warm the unopened solvent vial (Water for Injections) to room temperature or max. +37°C if necessary.

2.    Remove the protective caps from the powder vial and solvent vial (Fig. A) and disinfect the rubber stoppers of both vials.
3.    Open the protective cap from one end of the enclosed transfer needle by twisting, remove it and insert the needle through the rubber stopper of the solvent vial (Fig. B and C).
4.    Remove the protective cap from the other end of the transfer needle taking care not to touch the exposed end !
5.    Invert the solvent vial and insert the free end of the transfer needle through the rubber stopper of the powder vial (Fig. D). The solvent will be drawn into the powder vial by vacuum.
6.    Disconnect the two vials by removing the transfer needle from the powder vial (Fig. E). Gently swirl the powder vial to accelerate dissolution.
7.    Upon complete reconstitution of the powder, insert the enclosed aeration needle (Fig. F) and any foam will collapse. Remove the aeration needle.

Infusion:
1.    Open one end of the protective cap from the enclosed filter needle by twisting, remove it and fit the needle on to the sterile disposable syringe. Draw the solution into the syringe (Fig. G).
2.    Disconnect the filter needle from the syringe and slowly administer the solution intravenously with the enclosed infusion set (or the enclosed disposable needle).                                                                                                                                                                                                     Reconstitution of the powder for preparing a solution for infusion with the BaxJect II Hi- Flow:
1.    Warm the unopened solvent vial (Water for Injections) to room temperature (15°C to 25°C), for example by using a water bath for several minutes (max. 37°C) if necessary.

2.    Remove the protective caps from the powder vial and solvent vial and disinfect the rubber stoppers of both vials. Place the vials on an even surface.
3.    Open the packaging of the BAXJECT II Hi-Flow by pulling off the protective foil without touching the contents of the package (Fig. a). Do not remove the transfer system from the package at this point.
4.    Turn the package around and press the transparent plastic pin through the rubber stopper of the solvent vial (Fig. b). Now remove the packaging from the BAXJECT II Hi-Flow (Fig. c). Do not remove the blue protective cap from the BAXJECT II Hi-Flow.
5.    Now turn the system, consisting of the BAXJECT II Hi-Flow and the solvent vial, in such a way that the solvent vial is on top. Press the purple pin of the BAXJECT II Hi-Flow through the FEIBA vial. The solvent is drawn into the FEIBA vial by vacuum (Fig. d).
6.    Swirl, but do not shake the entire system gently until the powder is dissolved. Make sure that the FEIBA has been dissolved completely, as active material may otherwise be retained by the filter in the system.                                                                                                                                                                                                                                                                                               Infusion
1)    Remove the blue protective cap from the BAXJECT II Hi-Flow. Tightly connect the syringe to the BAXJECT II Hi-Flow. DO NOT DRAW AIR INTO THE SYRINGE. (Fig. e). In order to ensure tight connection between syringe and BAXJECT II Hi- Flow, the use of a luer lock syringe is highly recommended (turn syringe in clockwise direction until stop position when mounting).
2)    Invert the system so that the dissolved product is on top. Draw the dissolved product into the syringe by pulling the plunger back SLOWLY and ensure that the tight connection between BAXJECT II Hi-Flow and the syringe is maintained throughout the whole pulling process (Fig. f).
3)    Disconnect the syringe.
4)    If foaming of the product in the syringe occurs, wait until the foam is collapsed. Slowly administer the solution intravenously with the enclosed infusion set (or disposable needle).