KOATE-DVI Powder fo solution Ref.[50352] Active ingredients: Coagulation factor VIII

The reconstituted product must be administered intravenously by either direct syringe injection or drip infusion. The product must be administered within 3 hours after reconstitution.

General Approach to Treatment and Assessment of Treatment Efficacy

The dosages described below are presented as general guidance. It should be emphasized that the dosage of Koate-DVI required for hemostasis must be individualized according to the needs of the patient, the severity of the deficiency, the severity of the hemorrhage, the presence of inhibitors, and the Factor VIII level desired. It is often critical to follow the course of therapy with Factor VIII level assays.

The clinical effect of Koate-DVI is the most important element in evaluating the effectiveness of treatment. It may be necessary to administer more Koate-DVI than would be estimated in order to attain satisfactory clinical results. If the calculated dose fails to attain the expected Factor VIII levels, or if bleeding is not controlled after administration of the calculated dosage, the presence of a circulating inhibitor in the patient should be suspected. Its presence should be substantiated and the inhibitor level quantitated by appropriate laboratory tests.

When an inhibitor is present, the dosage requirement for Antihemophilic Factor (Human) is extremely variable and the dosage can be determined only by the clinical response. Some patients with low titer inhibitors (10 Bethesda Units) can be successfully treated with Factor VIII without a resultant anamnestic rise in inhibitor titer.(12) Factor VIII levels and clinical response to treatment must be assessed to insure adequate response. Use of alternative treatment products, such as Factor IX Complex concentrates, Antihemophilic Factor (Porcine) or Anti-Inhibitor Coagulant Complex, may be necessary for patients with high titer inhibitors. Immune tolerance therapy using repeated doses of Factor VIII concentrate administered frequently on a predetermined schedule may result in eradication of the Factor VIII inhibitor.(13,14) Most successful regimens have employed high doses of Factor VIII administered at least once daily, but no single dosage regimen has been universally accepted as the most effective. Consultation with a hemophilia expert experienced with the management of immune tolerance regimens is also advisable.

Calculation of Dosage

The in vivo elevation in Factor VIII level (percent of normal) can be estimated by multiplying the dose of Antihemophilic Factor (Human) per kilogram of body weight (IU/kg) by 2%. This method of calculation is based on clinical findings by Abildgaard et al,(15) and is illustrated in the following examples:

The dosage necessary to achieve hemostasis depends upon the type and severity of the bleeding episode, according to the following general guidelines:

Expected % Factor VIII increase (% of normal) = (# units administered x 2%/IU/kg) / body weight (kg)

Example for a 70 kg adult: (400 IU x 2%/IU/kg) / 70 k = 40%

or

Dosage required (IU) = [body weight (kg) x desired % Factor VIII increase (% of normal)] / 2%/IU/kg

Example for a 15 kg child: (15 kg x 100%) / 2%/IU/kg = 750 IU required

Mild Hemorrhage

Mild superficial or early hemorrhages may respond to a single dose of 10 IU per kg,(4) leading to an in vivo rise of approximately 20% in the Factor VIII level. Therapy need not be repeated unless there is evidence of further bleeding.

Moderate Hemorrhage

For more serious bleeding episodes (e.g., definite hemarthroses, known trauma), the Factor VIII level should be raised to 30%–50% by administering approximately 15-25 IU per kg. If further therapy is required, repeated doses of 10-15 IU per kg every 8-12 hours may be given.(16)

Severe Hemorrhage

In patients with life-threatening bleeding or possible hemorrhage involving vital structures (e.g., central nervous system, retropharyngeal and retroperitoneal spaces, iliopsoas sheath), the Factor VIII level should be raised to 80%-100% of normal in order to achieve hemostasis. This may be achieved in most patients with an initial Antihemophilic Factor (Human) dose of 40-50 IU per kg and a maintenance dose of 20-25 IU per kg every 8-12 hours.(17,18) For major surgical procedures, Factor VIII levels should be checked throughout the perioperative course to ensure adequate replacement therapy.

Surgery

For major surgical procedures, the Factor VIII level should be raised to approximately 100% by giving a preoperative dose of 50 IU/kg. The Factor VIII level should be checked to assure that the expected level is achieved before the patient goes to surgery. In order to maintain hemostatic levels, repeat infusions may be necessary every 6 to 12 hours initially, and for a total of 10 to 14 days until healing is complete. The intensity of Factor VIII replacement therapy required depends on the type of surgery and postoperative regimen employed. For minor surgical procedures, less intensive treatment schedules may provide adequate hemostasis.(17,18)

Prophylaxis

Factor VIII concentrates may also be administered on a regular schedule for prophylaxis of bleeding, as reported by Nilsson et al.(19)

Reconstitution

Vacuum Transfer

Note: Aseptic technique should be carefully followed. All needles and vial tops that will come into contact with the product to be administered via the intravenous route should not come in contact with any non-sterile surface. Any contaminated needles should be discarded by placing in a puncture proof container, and new equipment should be used.

1. After removing all items from the box, warm the sterile water (diluent) to room temperature (25°C, 77°F).
2. Remove shrink band from product vial. If the shrink band is absent or shows signs of tampering, do not use the product and notify Grifols Therapeutics LLC immediately.
3. Remove the plastic flip tops from each vial (Fig. A). Cleanse vial tops (grey stoppers) with alcohol swab and allow surface to dry. After cleaning, do not allow anything to touch the latex (rubber) stopper.
4. Carefully remove the plastic sheath from the short end of the transfer needle. Insert the exposed needle into the diluent vial to the hub. (Fig. B)
5. Carefully grip the sheath of the other end of the transfer needle and twist to remove it.
6. Invert the diluent vial and insert the attached needle into the vial of concentrate at a 45° angle (Fig. C). This will direct the stream of diluent against the wall of the concentrate vial and minimize foaming. The vacuum will draw the diluent into the concentrate vial.**
7. Remove the diluent bottle and transfer needle (Fig. D).
8. Immediately after adding the diluent, agitate vigorously for 10-15 seconds, (Fig. E1) then swirl continuously until completely dissolved (Fig. E2). Some foaming will occur, but attempt to avoid excessive foaming. The vial should then be visually inspected for particulate matter and discoloration prior to administration.
9. Clean the top of the vial of reconstituted Antihemophilic Factor (Human), Koatew-DVI, again with alcohol swab and let surface dry.
10. Attach the filter needle (from the package) to a sterile syringe. Withdraw the Koate-DVI solution into the syringe through the filter needle (Fig. F).
11. Remove the filter needle from the syringe and replace with an appropriate injection or butterfly needle for administration. Discard filter needle into a puncture proof container.
12. If the same patient is using more than one vial of Koate-DVI, the contents of multiple vials may be drawn into the same syringe through the filter needles provided.

^** If vacuum is lost in the concentrate vial during reconstitution, use a sterile syringe and needle to remove the sterile water from the diluent vial and inject it into the concentrate vial, directing the stream of fluid against the wall of the vial.

Rate of Administration

The rate of administration should be adapted to the response of the individual patient, but administration of the entire dose in 5 to 10 minutes is generally well-tolerated.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Koate-DVI should be stored under refrigeration (2–8°C; 36–46°F). Storage of lyophilized powder at room temperature (up to 25°C or 77°F) for 6 months, such as in home treatment situations, may be done without loss of Factor VIII activity. Freezing should be avoided as breakage of the diluent bottle might occur.

RX only.