BERIATE Powder and solvent for solution for injection / infusion Ref.[51144] Active ingredients: Coagulation factor VIII

Treatment should be under the supervision of a physician experienced in the treatment of haemophilia.

Treatment monitoring

During the course of treatment, appropriate determination of factor VIII levels is advised to guide the dose to be administered and the frequency of repeated infusions. Individual patients may vary in their response to factor VIII, demonstrating different half-lives and recoveries. Dose based on bodyweight may require adjustment in underweight or overweight patients. In the case of major surgical interventions in particular, precise monitoring of the substitution therapy by means of coagulation analysis (plasma factor VIII activity) is indispensable.

Patients should be monitored for the development of factor VIII inhibitors. See also section 4.4.

Posology

The dosage and duration of the substitution therapy depend on the severity of the factor VIII deficiency, on the location and extent of the bleeding and on the patient’s clinical condition.

The number of units of factor VIII administered is expressed in International Units (IU), which are related to the current WHO concentrate standard for factor VIII products. Factor VIII activity in plasma is expressed either as a percentage (relative to normal human plasma) or preferably in IU (relative to an International Standard for factor VIII in plasma).

One IU of factor VIII activity is equivalent to that quantity of factor VIII in one ml of normal human plasma.

On demand treatment

The calculation of the required dosage of factor VIII is based on the empirical finding that 1 IU factor VIII per kg body weight raises the plasma factor VIII activity by about 2% (2 IU/dl) of normal activity. The required dosage is determined using the following formula:

Required units = body weight [kg] x desired factor VIII rise [% or IU/dl] x 0.5.

The amount to be administered and the frequency of administration should always be oriented to the clinical effectiveness in the individual case.

In the case of the following haemorrhagic events, the factor VIII activity should not fall below the given plasma activity level (in % of normal or IU/dl) in the corresponding period. The following table can be used to guide dosing in bleeding episodes and surgery:

Prophylaxis

For long term prophylaxis against bleeding in patients with severe haemophilia A, the usual doses are 20 to 40 IU of factor VIII per kg body weight at intervals of 2 to 3 days. In some cases, especially in younger patients, shorter dosage intervals or higher doses may be necessary.

Paediatric population

Dosing in children is based on body weight and is therefore generally based on the same guidelines as for adults. The frequency of administration should always be oriented to the clinical effectiveness in the individual case. Some experience from treatment of children less than 6 years exists (see section 5.1).

Method of administration

For intravenous use.

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

The preparation should be warmed to room or body temperature before administration. Inject or infuse slowly intravenously at a rate which the patient finds comfortable. The injection or infusion rate should not exceed 2 ml per minute.

Observe the patient for any immediate reaction. If any reaction takes place that might be related to the administration of Beriate, the rate of infusion should be decreased or the infusion stopped, as required by the clinical condition of the patient (see also Section 4.4).

No symptoms of overdose with human coagulation factor VIII are known so far.

3 years.

Chemical and physical in-use stability of the reconstituted product has been demonstrated for 8 hours at 25°C. From a microbiological point of view the product should be used immediately. If it is not administered immediately, a storage in the vial shall not exceed 8 hours at room temperature. Once transferred into the syringe, the product should be used immediately (see also section 6.6).

Store in a refrigerator (2°C–8°C). Do not freeze. Keep the container in the outer carton in order to protect from light.

Within the shelf-life, Beriate may be stored at up to 25°C, not to exceed a cumulative storage period of 1 month. The single room temperature periods should be documented to comply with the overall 1 month period.

DO NOT expose the vials to direct heat. The vials must not be heated above body temperature (37ºC).

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

Immediate Containers

Injection vial of colourless glass (250 IU and 500 IU: Type I; 1000 and 2000 IU: Type II)), sealed under vacuum with rubber stopper (bromobutyl), aluminium cap and plastic disc (polypropylene).

Presentations

Box with 250 IU containing:

1 vial with powder
1 vial with 2.5 ml water for injections
1 filter transfer device 20/20

Administration set (inner box):

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

Box with 500 IU containing:

1 vial with powder
1 vial with 5 ml water for injections
1 filter transfer device 20/20

Administration set (inner box):

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

Box with 1000 IU containing:

1 vial with powder
1 vial with 10 ml water for injections
1 filter transfer device 20/20

Administration set (inner box):

1 disposable 10 ml syringe
1 venipuncture set
2 alcohol swabs
1 non-sterile plaster

Box with 2000 IU containing:

1 vial with powder
1 vial with 10 ml water for injections
1 filter transfer device 20/20

Administration set (inner box):

1 disposable 10 ml syringe
1 venipuncture set
2 alcohol swabs
1 non-sterile plaster

Not all pack sizes may be marketed.

Method of administration

General instructions:

• The solution should be clear or slightly opalescent. Occasionally, a few flakes or particles may appear in the vial. The filter included in the Mix2Vial removes these particles. This filtration does not affect dosage calculations. After filtering and withdrawal (see below) of the reconstituted product into the syringe, the product in the syringe should be inspected visually for particulate matter and discoloration prior to administration. Do not use solutions which are cloudy or contain residues while in the syringe (deposits/particles).
• Once the product is transferred into the syringe, it should be used immediately. Do not store the product in the syringe.
• Reconstitution and withdrawal must be carried out under aseptic conditions.

	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 carefully counterclockwise 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 counterclockwise.

For injection of Beriate the use of plastic disposable syringes is recommended as the ground glass surfaces of all-glass syringes tend to stick with solutions of this type.

Administer solution slowly intravenously (see section 4.2), taking care to ensure that no blood enters the syringe filled with product. Use the venipuncture kit that is supplied with the product, insert the needle into a vein. Let blood flow back to the end of the tube. Attach the syringe to the threaded, locking end of the venipuncture kit.

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