KCENTRA Powder for solution for infusion, lyophilized Ref.[50986] Active ingredients: Coagulation factor IX complex Protein C Protein S

For intravenous use after reconstitution only.

2.1 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 acute major bleeding or an urgent need for surgery and other invasive procedures.
• Individualize KCENTRA 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 Factors II, VII, IX and X, Proteins C and S is stated on the carton.
• Administer Vitamin K concurrently to patients receiving KCENTRA. Vitamin K is administered to maintain Vitamin K-dependent clotting factor levels once the effects of KCENTRA 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 KCENTRA.

Table 1. Dosage Required for Reversal of VKA Anticoagulation in Patients with acute major bleeding or 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 20–31 Factor IX units/mL after reconstitution. The actual potency for 500 unit vial ranges from 400-620 units/vial. The actual potency for 1000 unit vial ranges from 800-1240 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 KCENTRA, calculated as follows based on INR range of 4–6, see Table 1:

35 units of Factor IX/kg × 80 kg = 2,800 units of Factor IX required¹

Monitor INR and clinical response during and after treatment. In clinical trials, KCENTRA decreased the INR to ≤1.3 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)].

¹ 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).

2.2 Preparation and Reconstitution

• Reconstitute KCENTRA using aseptic technique with 20 mL (nominal potency 500 U kit) or 40 mL (nominal potency 1000 U kit) of Sterile Water for Injection (diluent) provided in the kit.
• Do not use KCENTRA beyond the expiration date on the vial label and carton.
• KCENTRA is for single-dose only. Contains no preservatives. Discard partially used vials.

2.2.105 SPL UNCLASSIFIED SECTION

Kcentra Reconstitution Instructions:

1. Ensure that the KCENTRA vial and diluent vial are at room temperature.

2. Remove flip caps from the KCENTRA and diluent vials.

3. Wipe the stoppers with the alcohol swab provided and allow to dry prior to opening the Mix2Vial package.

4. Open the Mix2Vial package by peeling off the lid (Fig. 1). Do not remove the Mix2Vial from the blister package.

Fig. 1:

5. Place the diluent 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 diluent vial stopper (Fig. 2).

Fig. 2:

6. 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 (Fig. 3).

Fig. 3:

7. Place the KCENTRA vial on an even and firm surface. Invert the diluent vial with the Mix2Vial set attached and push the spike of the transparent adapter end straight down through the KCENTRA vial stopper (Fig. 4). The diluent will automatically flow into the KCENTRA vial.

Fig. 4:

Note: If the vacuum in the KCENTRA vial is accidentally lost during reconstitution with the Mix2Vial device, the transfer with the Mix2Vial will not work.

In this case, separate the set into two pieces as illustrated in Fig. 6 below; do not discard the diluent vial. Place the KCENTRA vial aside on a flat surface. Remove the blue adapter end from the diluent vial of the Mix2Vial set (Fig. 5) by lifting and bending the blue adapter to the side until it disconnects from the diluent vial.

For reconstitution:

• Using a separate sterile needle and syringe, withdraw the remaining diluent. Remove the needle from the syringe.
• Attach the syringe to the transparent adapter of the KCENTRA vial as illustrated in Fig. 8 below, and transfer the entire diluent volume into the KCENTRA vial. Remove syringe.
• Gently swirl the KCENTRA vial to ensure the product is fully dissolved. Do not shake.
• Proceed to step 10.

Fig. 5:

8. With one hand, grasp the KCENTRA-side of the Mix2Vial set and with the other hand grasp the diluent-side and unscrew the set carefully counterclockwise into two pieces (Fig. 6). Discard the diluent vial with the blue Mix2Vial adapter attached.

Fig. 6:

9. Gently swirl the KCENTRA vial with the transparent adapter attached until the substance is fully dissolved (Fig. 7). Do not shake.

Fig. 7:

10. Draw air into an empty, sterile syringe. While the KCENTRA vial is upright, connect the syringe to the Mix2Vial’s Luer Lock fitting by screwing clockwise. Inject air into the KCENTRA vial (Fig. 8).

Fig. 8:

11. While keeping the syringe plunger pressed, turn the system upside down and draw the solution into the syringe by pulling the plunger back slowly (Fig. 9).

Fig. 9:

12. 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 (Fig. 10). Attach the syringe to a suitable intravenous administration set.

Fig. 10:

13. After reconstitution, administration should begin promptly or within 4 hours.

14. If the same patient is to receive more than one vial, you may pool the contents of multiple vials. Use a separate unused Mix2Vial transfer set for each product vial.

2.3 Administration

• Do not mix KCENTRA with other medicinal products; administer through a separate infusion line.
• Visually inspect the reconstituted solution for particulate matter and discoloration prior to administration whenever solution and container permit. Reconstituted KCENTRA solution should be colorless, clear to slightly opalescent, and free from visible particles. Do not use if the solution is cloudy, discolored, or contains particulates.
• Use aseptic technique when administering KCENTRA.
• Administer at room temperature.
• 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, as there is a possibility of fibrin clot formation.

Prior to Reconstitution:

• KCENTRA is for single-dose only. Contains no preservatives.
• Store KCENTRA between 2–25°C (36–77°F), this includes room temperature, not to exceed 25°C (77°F). Do not freeze.
• KCENTRA is stable for 36 months from the date of manufacture, up to the expiration date on the carton and vial labels.
• Do not use KCENTRA beyond the expiration date on the vial label and carton.
• Store the vial in the original carton to protect it from light.

After Reconstitution:

KCENTRA must be used within 4 hours following reconstitution. Reconstituted KCENTRA can be stored at 2–25°C. If cooled, the solution should be warmed to 20–25°C prior to administration. Do not freeze. Discard partially used vials.