FIBROGAMMIN Powder and solvent for solution for injection Ref.[9446] Active ingredients: Coagulation factor XIII

Posology

1 ml is equivalent to 62.5 IU, and 100 IU are equivalent to 1.6 ml, respectively.

Important: The amount to be administered and the frequency of administration should always be orientated towards clinical efficacy in the individual case.

Dosage

The dosing regimen should be individualised based on body weight, laboratory values, and the patient’s clinical condition.

Routine prophylaxis dosing schedule for treatment of congenital FXIII deficiency

Initial dose

40 International Units (IU) per kg body weight

The injection rate should not exceed 4 ml per minute.

Subsequent dosing

Dosing should be guided by the most recent trough FXIII activity level, with dosing every 28 days (4 weeks) to maintain a trough FXIII activity level of approximately 5 to 20%.

Recommended dosing adjustments of ± 5 IU per kg should be based on trough FXIII activity levels as shown in Table 1 and the patient’s clinical condition.

Dosing adjustments should be made on the basis of a specific, sensitive assay used to determine FXIII levels.

An example of dose adjustment using the standard Berichrom FXIII activity assay is outlined in Table 1 below.

Table 1. Dose adjustment using the Berichrom FXIII activity assay:

The potency expressed in units is determined using the Berichrom FXIII activity assay, referenced to the current International Standard for Blood Coagulation Factor XIII, Plasma. Therefore, a unit is equivalent to an International Unit.

Prophylaxis prior to surgery

After the patient’s last routine prophylactic dose, if a surgery is scheduled:

• Between 21 and 28 days later – administer the patient’s full prophylaxis dose immediately prior to surgery and the next prophylactic dose should be given 28 days later.
• Between 8 and 21 days later – an additional dose (full or partial) may be administered prior to surgery. The dose should be guided by the patient’s FXIII activity levels and clinical condition and should be adjusted according to the half-life of Fibrogammin.
• Within 7 days of last dose – additional dosing may not be needed.

Adjustments to dosing may be different from these recommendations and should be individualised, based on FXIII activity levels and the patient’s clinical condition. All patients should be monitored closely during and after surgery.

It is recommended to monitor the increase in FXIII-activity with a FXIII assay. In the case of major surgery and severe haemorrhage, the aim is to obtain values within the normal range for healthy people, i.e. 0.7-1.4 IU/ml.

Paediatric population

The posology and method of administration in children and adolescents is based on body weight and is therefore generally based on the same guidelines as for adults. The dose and/or frequency of administration for each individual should always be guided by the clinical effectiveness and FXIII activity levels. (Please also refer to sections 5.1 and 5.2.)

Elderly population

The posology and method of administration in elderly people (>65 years) has not been established in clinical studies.

Method of administration

For instructions on reconstitution of the medicinal product before administration, see section 6.6.

After reconstitution the solution should be clear or slightly opalescent. The preparation should be warmed to room or body temperature before administration. Slowly inject or infuse intravenously into a separate injection/infusion line (provided with the product) at a rate which the patient finds comfortable. The injection or infusion rate should not exceed approximately 4ml per minute.

Observe the patient for any immediate reaction. If any reaction takes place that might be related to the administration of Fibrogammin, the rate of infusion should be decreased or the infusion stopped, as required by the clinical condition of the patient.

No cases of overdose have been reported.

Shelf life: 3 years.

Do not use after the expiry date given on the pack and container.

Do not freeze reconstituted solution.

Chemical and physical in-use stability has been demonstrated for 24 hours at 25°C.

From a microbiological point of view, unless the method of opening and reconstitution precludes the risk of microbial contamination, the product should be used immediately. If not used immediately, storage times and conditions are the responsibility of the user.

Store in a refrigerator (+2 to +8 °C).

Do not freeze.

Keep the vial in the outer carton in order to protect from light.

For storage conditions after reconstitution of the medicinal product, see section 6.3.

Vials

250 IU:

Powder: injection vial of colourless glass, sealed with a bromobutyl rubber stopper, aluminium cap and plastic disc.

Solvent (Water for Injections): vial of colourless glass

1250 IU:

Powder: injection vial of colourless glass, sealed with a bromobutyl rubber stopper, aluminium cap and plastic disc.

Solvent (Water for Injections): vial of colourless glass.

Presentations

Pack with 250 IU:

1 vial with powder
1 vial with 4 ml Water for Injections
1 filter transfer device 20/20 (Mix2Vial)

Administration set (inner box):

1 disposable 5 ml syringe
1 venipuncture set
2 alcohol swabs
1 non-sterile plaster

Pack with 1250 IU:

1 vial with powder
1 vial with 20 ml Water for Injections
1 filter transfer device 20/20 (Mix2Vial)

Administration set (inner box):

1 disposable 20 ml syringe
1 venipuncture set
2 alcohol swabs
1 non-sterile plaster

General instructions

The solution should be clear or slightly opalescent. After filtering/withdrawal (see below) the reconstituted product should be inspected visually for particulate matter and discoloration prior to administration.

Reconstitution and withdrawal must be carried out under aseptic conditions.

Do not use solutions which are cloudy or contain residues (deposits/particles).

Reconstitution

Bring the solvent to room temperature. Ensure product and solvent vial flip caps are removed and the stoppers are treated with an antiseptic solution and allowed to dry prior to opening the Mix2Vial package.

1. Open the Mix2Vial package by peeling off the lid. Do not remove the Mix2Vial from the blister package!

2. Place the solvent vial on an even, clean surface and hold the vial tight. Take the Mix2Vial together with the blister package and push the spike of the blue adapter end straight down through the solvent vial stopper.

3. Carefully remove the blister package from the Mix2Vial set by holding at the rim, and pulling vertically upwards. Make sure that you only pull away the blister package and not the Mix2Vial set.

4. Place the product vial on an even and firm surface. Invert the solvent vial with the Mix2Vial set attached and push the spike of the transparent adapter end straight down through the product vial stopper.

The solvent will automatically flow into the product vial.

5. With one hand grasp the product-side of the Mix2Vial set and with the other hand grasp the solvent-side and unscrew the set counter-clockwise carefully into two pieces.

Discard the solvent vial with the blue Mix2Vial adapter attached.

6. Gently swirl the product vial with the transparent adapter attached until the substance is fully dissolved. Do not shake.

7. Draw air into an empty, sterile syringe.

While the product vial is upright, connect the syringe to the Mix2Vial’s Luer Lock fitting by screwing clockwise.

Inject air into the product vial.

Withdrawal and application:

8. While keeping the syringe plunger pressed, turn the system upside down and draw the solution into the syringe by pulling the plunger back slowly.

9. Now that the solution has been transferred into the syringe, firmly hold on to the barrel of the syringe (keeping the syringe plunger facing down) and disconnect the transparent Mix2Vial adapter from the syringe by unscrewing counter-clockwise.

Care should be taken that no blood enters the syringe filled with product, as there is a risk that the blood could coagulate in the syringe and fibrin clots could therefore be administered to the patient.

In case more than one vial of Fibrogammin is required, it is possible to pool several vials of Fibrogammin for a single infusion via a commercially available infusion device.

The Fibrogammin solution must not be diluted.

The reconstituted solution should be administered into a separate injection/infusion line (provided with the product) by slow intravenous injection, at a rate not exceeding 4 ml per minute.

Any unused product or waste material should be disposed of in accordance with local requirements.