Koate-DVI Dosage/Direction for Use

Each vial of Koate-DVI has the AHF(H) content in iu/vial stated on the label of the vial. The reconstituted product must be administered IV by either direct syringe injection or drip infusion. Koate-DVI must be administered within 3 hrs after reconstitution.
General Approach to Treatment and Assessment of Treatment Efficacy: The dosages described as follows 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 and 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 AHF(H) 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. Factor VIII levels and clinical response to treatment must be assessed to insure adequate response. Use of alternative treatment products eg, 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 FVIII concentrate administered frequently on a predetermined schedule may result in eradication of the FVIII inhibitor. Most successful regimens have employed high doses of FVIII 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 percent elevation in factor VIII level can be estimated by multiplying the dose of AHF(H) per kilogram of body weight (iu/kg) by 2%. This method of calculation is based on clinical findings by Abildgaard et al, and is illustrated in the following examples: See equations.

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The dosage necessary to achieve hemostasis depends upon the type and severity of the bleeding episode, according to the following general guidelines:
Mild Hemorrhage: Mild superficial or early hemorrhages may respond to a single dose of 10 iu/kg, 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 (eg, definite hemarthroses, known trauma), the factor VIII level should be raised to 30-50% by administering approximately 15-25 iu/kg. If further therapy is required, repeated doses of 10-15 iu/kg every 8-12 hrs may be given.
Severe Hemorrhage: In patients with life-threatening bleeding or possible hemorrhage involving vital structures (eg, 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 AHF [antihemophilic factor (human), Koate-DVI] dose of 40-50 iu/kg and a maintenance dose of 20-25 iu/kg every 8-12 hrs. 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 6-12 hrs initially, and for a total of 10-14 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.
Prophylaxis: Factor VIII concentrates may also be administered on a regular schedule for prophylaxis of bleeding, as reported by Nilsson et al.
Incorrect diagnosis, inappropriate dosage, method of administration, and biological differences in individual patients, could reduce the efficacy of Koate-DVI or even result in an ill effect following its use. It is important that Koate-DVI be stored properly, the directions for use be followed carefully during use, the risk of transmitting viruses be carefully weighed before the product is prescribed, and that plasma factor VIII levels be measured in initial treatment situations or if clinical response appears inadequate.
Reconstitution: Vacuum Transfer:
Warm the unopened diluent and the concentrate to room temperature (not more than 37°C, 99°F).
After removing the plastic flip-top caps, aseptically cleanse the rubber stoppers of both bottles.
Remove the protective cover from the plastic transfer-needle cartridge with tamperproof seal and penetrate the stopper of the diluent bottle.
Remove the remaining portion of the plastic cartridge, invert the diluent bottle and penetrate the rubber seal on the concentrate bottle with the needle at an angle. Alternate method of transferring sterile water: With a sterile needle and syringe, withdraw the appropriate volume of diluent and transfer to the bottle of lyophilized concentrate.
The vacuum will draw the diluent into the concentrate bottle. Hold the diluent bottle at an angle to the concentrate bottle in order to direct the jet of diluent against the wall of the concentrate bottle. Avoid excessive foaming.
After removing the diluent bottle and transfer needle, swirl vigorously until completely dissolved without creating excessive foaming.
After the concentrate powder is completely dissolved, withdraw solution into the syringe through the filter needle which is supplied in the package. Replace the filter needle with the administration set provided and inject IV.
If a patient is to receive >1 vial, the contents of 2 vials may be drawn into the same syringe; a separate unused filter needle should be used for each bottle, then the needle for IV injection should be attached to the syringe.
Rate of Administration: Should be adapted to the response of the individual patient, but administration of the entire dose in 5-10 min is generally well tolerated.