Feiba VH (Anti-Inhibitor Coagulant Complex) - Description and Clinical Pharmacology

DESCRIPTION

FEIBA VH Anti-Inhibitor Coagulant Complex, Vapor Heated (AICC) is a freeze-dried sterile human plasma fraction with Factor VIII inhibitor bypassing activity. In vitro, FEIBA VH AICC 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 AICC that shortens the APTT of a high titer Factor VIII inhibitor reference plasma to 50% of the blank value. The product is intended for intravenous administration.

FEIBA VH AICC contains Factors II, IX, and X, mainly non-activated, and Factor VII^1-3 mainly in the activated form. The product contains approximately equal unitages of Factor VIII inhibitor bypassing activity and Prothrombin Complex Factors. In addition, 1 - 6 units of Factor VIII coagulant antigen (FVIII C:Ag) per mL are present. The preparation contains only traces of factors of the kinin generating system. It contains no heparin.

Reconstituted FEIBA VH AICC contains 4 mg of trisodium citrate and 8 mg of sodium chloride per mL.

FEIBA VH Anti-Inhibitor Coagulant Complex, Vapor Heated has been prepared from Source Plasma and/or Plasma.

The product has been subjected to in-process virus inactivation where vapor is first applied for 10 hours at 60° ± 0.5°C and an excess pressure of 190 ± 20 mbar followed by 1 hour at 80°± 0.5°C and an excess pressure of 370 ± 30 mbar. (Refer to Clinical Pharmacology and Warnings sections).

CLINICAL PHARMACOLOGY

In a preclinical study to determine the virus inactivating efficacy of vapor heating, samples of bulk FEIBA IMMUNO Anti-Inhibitor Coagulant Complex were spiked with 2 × 10⁶/mL infectious units of HIV and subjected to vapor heat treatment. The residual virus titer was found to be less than 1 infectious unit/0.5 mL. A clinical study⁴ testing Antihemophilic Factor treated by a similar vapor heating procedure has shown none of 4 lots used in the study to produce non A, non B hepatitis in intensively followed patients naive to blood product administration.

The safety and efficacy of FEIBA IMMUNO AICC has been demonstrated by two prospective clinical trials^5-7. The first, conducted by Sixma and collaborators during 1979 and early 1980, was a randomized double-blind study comparing the effect of FEIBA IMMUNO AICC and PROTHROMPLEX IMMUNO (a non-activated prothrombin complex concentrate) in 15 patients with hemophilia A and inhibitors to Factor VIII. A total of 150 bleeding episodes (primarily joint and musculoskeletal plus a few mucocutaneous) were treated. A single dose of 88 Units per kg of body weight was used uniformly for treatments with FEIBA IMMUNO AICC. The study showed that, based on subjective patient evaluation, FEIBA IMMUNO AICC was fully effective in 41.0% and partly effective in 24.6% of episodes (i.e. combined effectiveness of 65.6%), while PROTHROMPLEX IMMUNO was rated fully effective in 25.0% and partly effective in 21.4% of episodes (i.e. combined effectiveness of 46.4%).

The second study with FEIBA IMMUNO AICC was a multiclinic study conducted by Hilgartner et al. It was designed to evaluate the efficacy of FEIBA IMMUNO AICC in the treatment of joint, mucous membrane, musculocutaneous and emergency bleeding episodes such as central nervous system hemorrhages and surgical bleedings. In 49 patients with inhibitor titers of greater than 5 Bethesda Units (from nine co-operating hemophilia centers), 489 single doses were given for the treatment of 165 bleeding episodes. The usual dosage was 50 Units per kg of body weight, repeated at 12-hour intervals (6-hour intervals in mucous membrane bleedings), if necessary. Bleeding was controlled in 153 episodes (93%). In 130 (78%) of the episodes, hemostasis was achieved with one or more infusions within 36 hours. Of these, 36% were controlled with one infusion within 12 hours. An additional 14% of episodes responded after more than 36 hours.

Of the 489 single doses, only 18 (3.7%) caused minor transient reactions in recipients. 10 out of 49 patients (20%) showed a rise in their inhibitor titers. In 5 of these patients (10%), the rise was tenfold or more. However, of these 10 patients, 3 had received Factor VIII or Factor IX concentrates within 2 weeks prior to treatment with FEIBA IMMUNO AICC. These anamnestic rises have not been observed to interfere with the efficacy of FEIBA IMMUNO Anti-Inhibitor Coagulant Complex.