FEIBA Powder and solvent for solution for infusion Ref.[4259] Active ingredients: Coagulation factor IX Coagulation factor VII Coagulation factor X Factor VIII inhibitor bypass activity Thrombin

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 50-100 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 50 – 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 50 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 50-100 U/kg body weight may be administered after 6-12 hours. As a postoperative maintenance dose, 50 -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

• 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 50-100 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 50% 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 Β 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

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.

Overdose of FEIBA may increase the risk of undesired events such as thromboembolism, DIC or myocardial infarction (see Section 4.4).

Two years.

Chemical and physical in-use stability has been demonstrated for 3 hours at room temperature. From a microbiological point of view, unless the method of reconstitution precludes the risk of microbial contamination (controlled and validated aseptic conditions), the product should be used immediately. If not used immediately, in-use storage times and conditions are the responsibility of the user.

Reconstituted product must not be refrigerated.

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 class II). The solvent is supplied in a vial made of surface treated, colorless glass (hydrolytic class I). The vials are closed by a stopper made of butyl rubber.

The package contains either:

• 1 vial with FEIBA 1000 U
• 1 vial with 20 ml sterilized 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 FEIB A 1000 U
• 1 vial with 20 ml sterilized Water for Injections
• 1 BAXJECT II Hi-Flow
• 1 disposable syringe
• 1 disposable needle
• 1 butterfly needle with clamp

Not all pack sizes 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 sterilized 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 μιη.

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 (sterilized 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. Β 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 (sterilized 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).

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