Balfaxar Dosage

Dosage

• Measurement of INR prior to treatment and close to the time of dosing is important because coagulation factors may be unstable in patients with need for an urgent surgery and other invasive procedures.
• Individualize BALFAXAR dosing based on the patient’s current pre-dose International Normalized Ratio (INR) value, and body weight (see Table 1 ).
• The actual potency per vial of Factor IX is stated on the carton. The potencies of Factors II, VII, IX and X, Proteins C and S are indicated as ranges.
• Administer Vitamin K concurrently to patients receiving BALFAXAR. Vitamin K is administered to maintain Vitamin K-dependent clotting factor levels once the effects of BALFAXAR have diminished.
• The safety and effectiveness of repeat dosing have not been established and it is not recommended.
• Dose ranging within pre-treatment INR groups has not been studied in randomized clinical trials of BALFAXAR.

Table 1 Dosage Required for Reversal of VKA Anticoagulation in Patients with Need for an Urgent Surgery/Invasive Procedure

* Dosing is based on body weight. Dose based on actual potency is stated on the vial, which will vary from 20-32 Factor IX units/mL after reconstitution. The actual potency for a 500 unit vial ranges from 400-640 units/vial. The actual potency for a 1000 unit vial ranges from 800-1280 units/vial.

† Units refer to International Units.

‡ Dose is based on body weight up to but not exceeding 100 kg. For patients weighing more than 100 kg, maximum dose should not be exceeded.

Example dosing calculation for 80 kg patient:

For example, an 80 kg patient with a baseline of INR of 5.0, the dose would be 2,800 Factor IX units of BALFAXAR, calculated as follows based on INR range of 4-6, see Table 1 :

35 units of Factor IX/kg x 80 kg = 2,800 units of Factor IX required*

* For a vial with an actual potency of 30 units/mL Factor IX, 93 mL would be given (2,800 U/30 U per mL = 93 mL).

Monitor INR and clinical response during and after treatment. In clinical trials, BALFAXAR decreased the INR to ≤1.5 within 30 minutes in most subjects. The relationship between this or other INR values and clinical hemostasis in patients has not been established [see Clinical Studies ( 14 )] .

Preparation and Reconstitution

BALFAXAR is provided with a transfer device (Nextaro ® ) for reconstitution of the lyophilized powder in diluent (sterile Water for Injection (sWFI)).

BALFAXAR is for single dose only. Do not re-use any of the components.

Inspect all components for physical integrity prior to use. Do not use products or components that appear damaged or broken.

Reconstitute BALFAXAR using aseptic technique for the procedure described below.

The product reconstitutes quickly (1 to 5 minutes) at room temperature (20°C to 25°C; 68°F to 77°F). As BALFAXAR contains no preservatives, the solution should be administered immediately after reconstitution, or within 8 hours, provided sterility is maintained. The reconstituted solution can be stored for up to 8 hours at room temperature (20°C to 25°C; 68°F to 77°F).

Instructions for Reconstitution:

Figure 1	1. Ensure that the lyophilized powder and diluent vials are at room temperature (20°C to 25°C, 68°F to 77°F). This temperature should be maintained during reconstitution. 2. Remove the flip caps from the lyophilized powder and diluent vials and disinfect the rubber stoppers with an alcohol swab and allow to dry. 3. Open the transfer device package by peeling off the lid ( Figure 1 ). To maintain sterility, do not remove the transfer device from the blister package and do not touch the spike.
Figure 2	4. Place the diluent vial on an even, clean surface and hold it firmly. Without removing the blister package, place the blue part of the transfer device on top of the diluent vial and press straight and firmly down until it snaps into place ( Figure 2 ). Do not twist while attaching.
Figure 3	5. While holding onto the diluent vial, carefully remove the blister package from the transfer device by pulling vertically upwards. Make sure to leave the transfer device attached firmly to the diluent vial ( Figure 3 ).
Figure 4	6. Place the lyophilized powder vial on an even, clean surface and hold it firmly. Take the diluent vial with the attached transfer device and turn it upside down. Place the white part of the transfer device connector on top of the powder vial and press firmly down until it snaps into place ( Figure 4 ). Do not twist while attaching. The diluent will flow automatically into the powder vial. Note: The transfer device must be attached to the diluent vial first and then to the lyophilized powder vial. Otherwise, loss of vacuum occurs, and transfer of the diluent does not take place. If diluent is not completely transferred to the lyophilized powder vial during this process, contact your Octapharma representative.
Figure 5	7. With both vials still attached, gently swirl the product vial until the product is fully dissolved. To avoid foam formation, do not shake the vial. BALFAXAR dissolves quickly at room temperature (20°C to 25°C; 68°F to 77°F) and is a clear solution that may be colorless to slightly blue. Unscrew the transfer device counterclockwise into two parts ( Figure 5 ). Do not touch the luer lock connector. 8. Dispose of the empty diluent vial together with the blue part of the transfer device.

Reconstituted products should be inspected visually for particulate matter. Do not use solutions that are cloudy or have deposits.

If the lyophilized powder fails to dissolve completely or an aggregate is formed, do not use the preparation.

After reconstitution, administration should begin promptly or within 8 hours, provided sterility is maintained.

If the same patient is to receive more than one vial, you may pool the contents of multiple vials, provided sterility is maintained. Use a separate unused transfer device for the reconstitution of each product vial.

Administration

BALFAXAR is for intravenous use after reconstitution only.

Do not mix with other medicinal products; administer through a separate infusion line. The infusion line may be flushed with normal saline before and after administration of BALFAXAR.

Instructions for Infusion:

Figure 6	1. Attach a syringe to the luer lock outlet on the white part of the transfer device (Figure 6).
Figure 7	2. Turn the vial upside down and draw the solution into the syringe ( Figure 7 ).
Figure 8	3. Once the solution has been transferred, firmly hold the barrel of the syringe (keeping the syringe plunger facing down) and remove the syringe from the transfer device ( Figure 8 ). 4. Dispose of the white part of the transfer device together with the empty vial. 5.Attach a suitable administration set to the luer adapter of the syringe. 6.Disinfect the intended injection site appropriately. 7.Administer by intravenous infusion at a rate of 0.12 mL/kg/min (~3 units/kg/min), up to a maximum rate of 8.4 mL/min (~210 units/min). No blood should enter the syringe due to the risk of fibrin clot formation.

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