FEIBA® VH IMMUNO
Human Plasma Factor VIII Inhibitor
Coagulant Complex Anti-inhibitor
Description: Feiba VH Immuno, is a freeze-dried sterile human plasma fraction with Factor VIII inhibitor bypassing activity. In vitro, Feiba VH Immuno shortens the activated partial thromboplastin time (APTT) of plasma containing Factor VIII inhibitor. Factor VIII inhibitor bypassing activity is expressed in arbitrary units. One Immuno Unit of activity is defined as that amount of Feiba VH Immuno which shortens the APTT of a high titer Factor VIII inhibitor reference plasma to 50% of the blank value. The product is intended for i.v. administration.
It contains Factors II, IX, and X, mainly non-activated, and Factor VII mainly in the activated form. The product contains approximately equal unitages of Factor VIII inhibitor bypassing activity and Prothrombin Complex Factors. In addition, 1 to 6 units of Factor VIII coagulant antigen (F VIII C: Ag)/mL are present. The preparation contains only traces of factors of the kinin generating system. It contains no heparin.
Feiba VH Immuno has been prepared from Source Plasma and/or Fresh Frozen Plasma. All units of plasma used in the manufacture have been tested for hepatitis surface antigen (HBSAg) and for anti-HIV-III by FDA approved methods and found nonreactive.
The product has been subjected to in-process virus inactivation where vapor is first applied for 10 hours at 60°C and an excess pressure of 190±20 mbar followed by 1 hour at 80°C and an excess pressure of 370±30 mbar (see Warnings).
Indications And Clinical Uses: For the control of spontaneous bleeding episodes or to cover surgical interventions in hemophilia A and B patients with inhibitors.
In addition, its use has been described in a few nonhemophiliacs with acquired inhibitors to Factors VIII, XI, and XII. It has been reported to be effective in a patient with von Willebrand’s disease with an inhibitor.
Clinical experience suggests that patients with a Factor VIII inhibitor titer of less than 5 B.U. may be successfully treated with Antihemophilic Factor. Patients with titers ranging between 5 and 10 B.U. may either be treated with Antihemophilic Factor or with this product. Cases with Factor VIII inhibitor titers greater than 10 B.U. have generally been refractory to treatment with Antihemophilic Factor.
Contra-Indications: In patients who are known to have a normal coagulation mechanism.
Manufacturers’ Warnings In Clinical States: This product must be used only in patients with circulating inhibitors to 1 or more coagulation factors and should not be used for the treatment of bleeding episodes resulting from coagulation factor deficiencies. It should not be given to patients with significant signs of disseminated intravascular coagulation (DIC) or fibrinolysis.
It is prepared from large pools of human plasma. Each unit of plasma used in the manufacture of this product has been tested and found nonreactive for HBsAg and HIV antibody by FDA approved tests. In addition, this product has been subjected to a vapor heat treatment during the manufacturing process to reduce the risk of transmitting viral infections. It must be emphasized that no procedure has been shown to be totally effective in eliminating viral infectivity from this product.
It has been reported that Feiba VH Immuno and antifibrinolytics have been given simultaneously without complications. It is, however, recommended not to use antifibrinolytics until 12 hours after the administration of Feiba VH Immuno.
Anamnestic responses with rise in Factor VIII inhibitor titer have been observed in 20% of the cases.
Precautions: If clinical signs of intravascular coagulation occur, which include changes in blood pressure, pulse rate, respiratory distress, chest pain and cough, the infusion should be stopped promptly and the patient monitored for DIC by appropriate laboratory tests. Laboratory indications of DIC are decreased fibrinogen, decreased platelet count, and/or presence of fibrin-fibrinogen degradation products (FDP). Other indications of DIC include significantly prolonged thrombin time, prothrombin time, or partial thromboplastin time.
Tests used to control efficacy such as APTT, WBCT, and TEG do not correlate with clinical improvement. For this reason, attempts at normalizing these values by increasing the dose of Feiba VH Immuno may not be successful and are strongly discouraged because of the potential hazard of producing DIC by overdosage.
Pregnancy: Animal reproduction studies have not been conducted with this product. It is also not known whether it can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. It should be given to a pregnant woman only if clearly needed.
Children: No data are available regarding its use in newborns.
Adverse Reactions: After application of high doses (single infusion of more than 100 units/kg body weight and daily doses of 200 units/kg) of Feiba VH, laboratory and/or clinical signs of DIC have occasionally been observed. For this reason, patients receiving more than 100 units/kg must be monitored continually for signs of accelerated coagulation.
As with all human plasma products, any kind of allergic reaction may be seen, ranging from mild, short-term urticarial rashes to severe anaphylactoid reactions.
Administration should be discontinued immediately, if such signs appear. Allergic reactions should be treated with antihistamines and glucocorticoids. Shock should be treated in the usual way.
Dosage And Administration: Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
Clinical trials have demonstrated that the response to treatment with Feiba may differ from patient to patient with no correlation to the patient’s inhibitor titer. Response may also vary between different types of hemorrhage (e.g., joint hemorrhage vs CNS hemorrhage).
As a general guideline a dosage range of 50 to 100 units/kg is recommended. However, care should be taken to distinguish between the following 4 indications, all of which have undergone careful clinical evaluation:
Joint Hemorrhage: 50 units/kg is recommended at 12-hour intervals, which may be increased to doses of 100 units/kg at 12-hour intervals.
Treatment should be continued until clear signs of clinical improvement appear, such as relief of pain, reduction of swelling or mobilization of the joint.
Mucous Membrane Bleeding: 50 units/kg is recommended to be given at 6-hour intervals under careful monitoring (visible bleeding site, repeated measurements of the patient’s hematocrit). Again, if hemorrhage does not stop, the dose may be increased to 100 units/kg at 6-hour intervals. However, 2 such administrations or 200 units/kg a day should not be exceeded.
Soft Tissue Hemorrhage: For serious soft tissue bleeding, such as retroperitoneal bleeding, doses of 100 units/kg at 12-hour intervals are recommended. A daily dosage of 200 units/kg should not be exceeded.
Other Severe Hemorrhages: Severe hemorrhages, such as CNS bleedings, have been effectively treated with doses of 100 units/kg at 12-hour intervals. Sometimes, Feiba VH may be indicated at 6-hour intervals until clear clinical improvement is achieved.
Do not refrigerate after reconstitution.
After complete reconstitution the injection or infusion should be commenced as promptly as practicable, but must be completed within 3 hours following reconstitution.
The solution must be given by i.v. injection or i.v. drip infusion and the maximum injection or infusion rate must not exceed 2 units/kg/minute. In a patient with a body weight of 75 kg, this corresponds to an infusion rate of 2.5 to 7.5 mL/minute depending on the number of units/vial (see label on vial).
Availability And Storage: Freeze-dried powder, accompanied by a suitable volume of sterile water for injection, USP, a sterile double-ended needle, and a sterile filter needle. The number of Immuno Units of human plasma factor VIII inhibitor bypassing activity is stated on the label of each bottle. Store at refrigerator temperature (2 to 8°C). Avoid freezing, which may damage the diluent bottle.