Indications for: FEIBA
To control and prevent bleeding episodes, perioperative management, or as routine prophylaxis to prevent or reduce the frequency of bleeding episodes in Hemophilia A and B with inhibitors (see full labeling). Not for treating bleeding episodes due to coagulation factor deficiencies in the absence of inhibitors to factor VIII or IX.
Control and Prevention of Bleeding Episodes
The efficacy of Feiba in the treatment of bleeding episodes has been demonstrated by 2 prospective clinical trials.
Trial 1 was a multicenter, randomized, double-blind trial comparing the effect of Feiba and a non-activated prothrombin complex concentrate in 15 patients with hemophilia A and inhibitors to factor VIII. A total of 150 bleeding episodes including 117 joints, 20 musculoskeletal and 4 mucocutaneous bleeds, were treated. A single dose of 88 units/kg was used uniformly for treatments with Feiba. A second treatment was allowed for muscle bleeds after 12 hours and 6 hours after mucocutaneous bleeds, if necessary. Patients and investigators were asked to rate hemostatic efficacy based on a scale of effective, partially effective, not effective or not sure. The criteria for evaluation of the effectiveness were severity of pain, subjective improvement, circumference of muscle or joint, restriction of joint mobility, cessation of open bleeding, start of rebleeding and quantity and nature of analgesics. Feiba was effective in 41% and partly effective in 25% of episodes (ie, combined effectiveness of 66%), while prothrombin complex concentrate was rated effective in 25% and partly effective in 21% of episodes (ie, combined effectiveness of 46%).
Trial 2 was a multicenter randomized, prospective trial. This trial was conducted in 44 hemophilia A patients with inhibitors, 3 hemophilia B patients with inhibitors, and 2 acquired factor VIII inhibitor patients. It was designed to evaluate the efficacy of Feiba in the treatment of joint, mucous membrane, musculocutaneous and emergency bleeding episodes such as central nervous system hemorrhages and surgical bleedings. Forty-nine (49) patients with inhibitor titers of >5 BU were enrolled from 9 co-operating hemophilia centers. Patients were treated with 50 units/kg, repeated at 12-hour intervals (6-hour intervals in mucous membrane bleedings), if necessary. A total of 489 infusions were given for the treatment of 165 bleeding episodes (102 joint, 33 muscle and soft tissue, 20 mucous membrane, and 10 emergency bleeds, including 3 central nervous system bleeds and 4 surgical procedures). Bleeding was controlled in 153 episodes (93%). In 130 (78%) of the episodes, hemostasis was achieved with 1 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.
In a multicenter, open-label, prospective, randomized clinical trial comparing patients receiving Feiba for prophylaxis with patients receiving Feiba for on-demand treatment, 36 hemophilia A and B patients with inhibitors to factor VIII or IX were analyzed in the intent-to-treat analysis. Patients were randomized to receive 12 months of prophylactic or on-demand treatment with Feiba. Seventeen patients randomized to the prophylaxis arm received 85 units/kg of Feiba every other day. Nineteen patients randomized to the on-demand arm received Feiba for the treatment of acute bleeding episodes per the dose and dosing regimen recommended. Target joints were defined as ≥4 bleeding episodes within 6 months. In this trial, ankles, knees, elbows and hips were target joint locations. Preexisting target joints were not considered as new target joints.
Hemostatic efficacy for treatment of acute bleeds was evaluated at 6 and 24 hours according to a pre-specified four-point scale of excellent, good, fair, or none. An evaluation of “none” was considered a treatment failure. The criteria for evaluation of the effectiveness were relief of pain, cessation of bleeding, and number of infusions required to treat a bleed.
A total of 825 bleeding episodes were reported including 196 that occurred during prophylaxis and 629 that occurred during on-demand therapy. A majority (78%) of the 794 bleeding episodes that were rated for efficacy were treated with 1 or 2 infusions. Hemostatic efficacy was rated as excellent or good for 74% of bleeding episodes rated at 6 hours post infusion and for 87% of the bleeding episodes at 24 hours post infusion. A total of 19 (2.4%) bleeds were rated as “none” at 6 hours post infusion; 1 bleed (0.1%) was rated “none” at 24 hours.
Hemostatic efficacy for routine prophylaxis was evaluated against patients who received on-demand therapy.
The overall median annual bleed rate (ABR) for the on-demand arm was 28.7 compared to 7.9 for the prophylaxis arm, which represents a 72% reduction in median ABR with prophylaxis. When analyzed by site (eg, joint, non-joint) and cause of bleeding (eg, spontaneous, traumatic), prophylactic treatment with Feiba resulted in a >50% reduction in ABR. There were fewer patients in the prophylaxis arm who developed new target joints (7 new target joints in 5 patients treated with prophylaxis compared to 23 new target joints in 11 patients in the on-demand arm). Target joints developed in 2 patients in the on-demand arm and 3 in the prophylaxis arm who did not have reported target joints at trial enrollment. A total of 3 of 17 (18%) patients had no bleeding episodes on prophylaxis. In the on-demand arm, all patients experienced a bleeding episode.
Adults and Children:
Infusion rate: ≤2units/kg/min. Joint hemorrhage: 50–100units/kg every 12hrs until improved. Mucous membrane bleeding: 50–100units/kg every 6hrs for at least 1 day or until resolved. Soft tissue hemorrhage: 100units/kg every 12hrs until resolved. Other severe hemorrhage (eg, CNS bleeds): 100units/kg every 6–12hrs until resolved. Preoperative: 50–100units/kg once immediately prior to surgery. Postoperative: 50–100units/kg every 6–12hrs until resolved and healed. Routine prophylaxis: 85units/kg every other day. All: Max 200units/kg per day (100units/kg per dose).
Hypersensitivity to factors of the kinin generating system. Disseminated intravascular coagulation (DIC). Acute thrombosis or embolism (including myocardial infarction).
Embolic and thrombotic events.
Increased risk of thromboembolic events esp. after high-doses (>200units/kg/day) and/or in patients with thrombotic risk factors (eg, DIC, atherosclerosis, crush injury, septicemia, concomitant recombinant factor VIIa). Monitor patients receiving doses >100units/kg for DIC development, acute coronary ischemia, and signs/symptoms of other thromboembolic events; discontinue if occurs and treat. Discontinue if hypersensitivity reactions occur. Contains human plasma; monitor for possible infection transmission. Elderly. Neonates. Pregnancy (Cat.C). Nursing mothers.
Coagulation factor complex.
Separate systemic antifibrinolytics by 12hrs.
Anemia, diarrhea, hemarthrosis, hep B surface antibody positive, nausea, vomiting; hypersensitivity, thromboembolic events (eg, stroke, DVT, PE).
Report all infections suspected to be transmitted by Feiba to (800) 423-2862.
Generic Drug Availability:
Single-dose vials—1 (w. diluent, transfer device)