Anti-Inhibitor Coagulant Complex

FDA Drug Information • Also known as: Feiba

Brand Names: Feiba
Dosage Form: KIT
Product Type: HUMAN PRESCRIPTION DRUG

⚠ Boxed Warning (Black Box)

WARNING: EMBOLIC and THROMBOTIC EVENTS Thromboembolic events have been reported during postmarketing surveillance following infusion of FEIBA, particularly following the administration of high doses and/or in patients with thrombotic risk factors. Monitor patients receiving FEIBA for signs and symptoms of thromboembolic events. WARNING: EMBOLIC and THROMBOTIC EVENTS See full prescribing information for complete boxed warning. Thromboembolic events have been reported during postmarketing surveillance, particularly following the administration of high doses and/or in patients with thrombotic risk factors. Monitor patients receiving FEIBA for signs and symptoms of thromboembolic events ( 5.1 , 6.2 ).

Description

11 DESCRIPTION FEIBA (Anti-Inhibitor Coagulant Complex) is a freeze-dried sterile human plasma fraction with factor VIII inhibitor bypassing activity to be reconstituted for intravenous administration. Factor VIII inhibitor bypassing activity is expressed in arbitrary units. One unit of activity is defined as that amount of FEIBA that shortens the aPTT of high titer factor VIII inhibitor reference plasma to 50% of the blank value. FEIBA contains mainly non-activated factors II, IX, and X and mainly activated factor VII. It contains approximately equal unitages of factor VIII inhibitor bypassing activity and prothrombin complex factors. In addition, the preparation contains 1-6 units of factor VIII coagulant antigen (FVIII C:Ag) per mL. The product contains traces of factors of the kinin generating system. It contains no heparin. Reconstituted FEIBA contains 4 mg of trisodium citrate and 8 mg of sodium chloride per mL. FEIBA is manufactured from large pools of human plasma. Screening against potentially infectious agents begins with the donor selection process and continues throughout plasma collection and plasma preparation. Each individual plasma donation used in the manufacture of FEIBA is collected at FDA approved blood establishments and is tested by FDA licensed serological tests for Hepatitis B Surface Antigen (HBsAg), and for antibodies to Human Immunodeficiency Virus (HIV-1/HIV-2) and Hepatitis C Virus (HCV) Mini-pools of the plasma are tested and found negative for the presence of HIV-1 and HCV by FDA licensed Nucleic Acid Testing (NAT). To reduce the risk of viral transmission, the manufacturing process of FEIBA includes two dedicated and independent virus removal/inactivation steps namely 35 nm nanofiltration and a vapor heat treatment process. In addition, the DEAE-Sephadex adsorption contributes to the virus safety profile of FEIBA. In vitro spiking studies have been used to validate the capability of the manufacturing process to remove and inactivate...

What Is Anti-Inhibitor Coagulant Complex Used For?

1 INDICATIONS AND USAGE FEIBA is an Anti-Inhibitor Coagulant Complex indicated for use in hemophilia A and B patients with inhibitors for: Control and prevention of bleeding episodes Perioperative management Routine prophylaxis to prevent or reduce the frequency of bleeding episodes. FEIBA is not indicated for the treatment of bleeding episodes resulting from coagulation factor deficiencies in the absence of inhibitors to coagulation factor VIII or coagulation factor IX. FEIBA is an Anti-Inhibitor Coagulant Complex indicated for use in hemophilia A and B patients with inhibitors for: Control and prevention of bleeding episodes. Perioperative management. Routine prophylaxis to prevent or reduce the frequency of bleeding episodes. FEIBA is not indicated for the treatment of bleeding episodes resulting from coagulation factor deficiencies in the absence of inhibitors to factor VIII or factor IX. ( 1 )

Dosage and Administration

2 DOSAGE AND ADMINISTRATION For intravenous use after reconstitution only. For intravenous use after reconstitution only ( 2 ) Each vial of FEIBA contains the labeled amount of factor VIII inhibitor bypassing activity in units. ( 2.1 ) Type of Bleeding Dose (unit/kg) Frequency/Duration Control and Prevention of Bleeding 50 - 100 Determined by the type of bleeding episode Perioperative Management 50 - 100 Determined by the type of surgical intervention Routine Prophylaxis 85 Every other day Maximum injection or infusion rate must not exceed 10 units per kg of body weight per minute. ( 2.3 ) 2.1 Dose A guide for dosing FEIBA is provided in Table 1. Table 1: Dosing Guidelines Dose (unit/kg) Frequency of Doses (hours) Duration of Therapy Control and Prevention of Bleeding Joint Hemorrhage 50 – 100 12 Until pain and acute disabilities are improved. Mucous Membrane Bleeding 50 – 100 6 At least 1 day or until bleeding is resolved. Soft Tissue Hemorrhage (e.g., retroperitoneal bleeding) 100 12 Until resolution of bleed. Other Severe Hemorrhage (e.g., CNS bleeds) 100 6 – 12 Until resolution of bleed. Perioperative Management Preoperative 50 – 100 One time dose Immediately prior to surgery. Postoperative 50 – 100 6 – 12 Until resolution of bleed and healing are achieved. Routine Prophylaxis 85 Every other day Dosage and duration of treatment depend on the location and extent of bleeding, and the patient's clinical condition. Careful monitoring of replacement therapy is necessary in cases of major surgery or life-threatening bleeding episodes. Each vial of FEIBA contains the labeled amount of factor VIII inhibitor bypassing activity in units. Base the dose and frequency of FEIBA on the individual clinical response. Clinical response to treatment with FEIBA may vary by patient and may not correlate with the patient's inhibitor titer. Record the name of the patient and batch number of the product in order to maintain a link between the patient and the batch of the product. Do not exceed a single dose of 100 units per kg body weight or a daily dose of 200 units per kg body weight [see Warnings and Precautions (5.1) ] . 2.2 Preparation and Reconstitution Use aseptic technique throughout the entire reconstitution process. If the patient uses more than one vial per injection, reconstitute each vial according to the following instructions. Allow the vials of FEIBA and Sterile Water for Injection (diluent) to reach room temperature, if refrigerated. Remove the plastic caps from the concentrate and diluent vials. Wipe the stoppers of both vials with a sterile alcohol swab and allow them to dry prior to use. Open the package of BAXJECT II Hi-Flow device by peeling away the lid completely without touching the inside (Fig. A). Do not remove the device from the package. Do not touch the clear spike. Place the diluent vial on a flat and solid surface. Turn the package over and insert the clear plastic spike through the diluent stopper by pressing straight down (Fig. B)....

Side Effects (Adverse Reactions)

6 ADVERSE REACTIONS The most frequently reported adverse reactions observed in >5% of subjects in the prophylaxis trial were anemia, diarrhea, hemarthrosis, hepatitis B surface antibody positive, nausea, and vomiting. The serious adverse reactions seen with FEIBA are hypersensitivity reactions and thromboembolic events, including stroke, pulmonary embolism and deep vein thrombosis. The most common adverse reactions observed in >5% of subjects were anemia, diarrhea, hemarthrosis, hepatitis B surface antibody positive, nausea, and vomiting. ( 6.1 ) The serious adverse drug reactions are hypersensitivity and thromboembolic events, including stroke, pulmonary embolism, and deep vein thrombosis. ( 5.1 , 5.2 , 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Takeda Pharmaceuticals U.S.A., Inc. at 1-877-TAKEDA-7 (1-877-825-3327) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. The safety assessment of FEIBA is based on the review of the data from two prospective clinical trials in which FEIBA was used for the treatment of acute bleeding episodes and a prospective trial that compared the use of FEIBA prophylactically versus on-demand treatment. The adverse reactions reported from two prospective clinical trials in which FEIBA was used for the treatment of acute bleeding episodes were chills, chest pain, chest discomfort, dizziness, dysgeusia, dyspnea, hypoesthesia, increase of inhibitor titer (anamnestic response), nausea, pyrexia, and somnolence. Specifically, the first trial was a multicenter randomized, double-blind trial in 15 hemophilia A subjects with inhibitors to factors VIII. The second trial was a multicenter FEIBA study conducted in 44 hemophilia A subjects with inhibitors, 3 hemophilia B subjects with inhibitors and 2 acquired factor VIII inhibitor subjects. Of the 489 infusions used to treat acute bleeds during the second trial, 18 (3.7%) caused minor transient reactions of chills, fever, nausea, dizziness and dysgeusia. Out of 49 subjects, 10 (20%) had a rise in their inhibitor titers after treatment with FEIBA. Five of these subjects (50%) had increases that were tenfold or more, and 3 (30%) of these subjects received factor VIII or IX concentrates within 2 weeks prior to treatment with FEIBA. These anamnestic rises were not associated with decreased efficacy of FEIBA. Table 2 lists the adverse reactions in >5% of subjects reported in the randomized, prospective prophylaxis trial comparing FEIBA prophylaxis with on-demand treatment in 36 hemophilia A and B subjects with inhibitors to factors VIII or IX 3 . The trial population included 33 (92%) subjects with hemophilia A and 3 (8.3%) subjects with hemophilia B. Four (11%) subjects were ≥7 to <12 years of age, 5 (14%) were ≥12 to <16 years of age, and 27 (75%) were ≥16 years of age. A total of 29 (80.6%) subjects were Caucasian, 3 (8.3%) Asian, 2 (5.6%) Black/African American, and 2 (5.6%) other. The subjects received a total of 4,513 infusions (3,131 for prophylaxis and 1,382 for on-demand). Table 2: Prophylaxis Study Adverse Reactions (ARs) in >5% of Subjects MedDRA System Organ Class Adverse Reaction Number of ARs Number of Subjects Percent of Subjects (N=36) Blood And Lymphatic System Disorders Anemia 2 2 5.6 Gastrointestinal Disorders Diarrhea 2 2 5.6 Nausea 2 2 5.6 Vomiting 2 2 5.6 Investigations Hepatitis B Surface Antibody Positive 4 4 11.1 Musculoskeletal And Connective Tissue Disorders Hemarthrosis 5 3 8.3 Table 3 lists the adverse reactions and infusion related adverse events reported in >5% of subjects in any of the three groups (50% Reduced Volume, Increased Rate 4 U/kg/min; 50% Reduced Volume, Increased Rate 10 U/kg/min; Overall 50% Reduced Volume) of...

Drug Interactions

7 DRUG INTERACTIONS Consider the possibility of thrombotic events when systemic antifibrinolytics such as tranexamic acid and aminocaproic acid are used. Use of antifibrinolytics within approximately 6 to 12 hours after the administration of FEIBA is not recommended. ( 7 ) 7.1 Concomitant Medications Consider the possibility of thrombotic events when systemic antifibrinolytics such as tranexamic acid and aminocaproic acid are used during treatment with FEIBA. No adequate and well-controlled studies of the combined or sequential use of FEIBA and recombinant factor VIIa antifibrinolytics, or emicizumab have been conducted. Use of antifibrinolytics within approximately 6 to 12 hours after the administration of FEIBA is not recommended. Clinical experience from an emicizumab clinical trial suggests that a potential drug interaction may exist with emicizumab when FEIBA was used as part of a treatment regimen for breakthrough bleeding 6 [see Warnings and Precautions (5.1) ] .

Contraindications

4 CONTRAINDICATIONS Known anaphylactic or severe hypersensitivity reactions to FEIBA or any of its components, including factors of the kinin generating system. Disseminated intravascular coagulation (DIC). Acute thrombosis or embolism (including myocardial infarction). History of anaphylactic or severe hypersensitivity reactions to FEIBA or any of its components, including factors of the kinin generating system. ( 4 ) Disseminated intravascular coagulation (DIC). ( 4 ) Acute thrombosis or embolism (including myocardial infarction). ( 4 )

Pregnancy and Breastfeeding

8.1 Pregnancy Risk Summary There are no data with FEIBA use in pregnant women to inform a drug-associated risk. There are no adequate and well-controlled studies in pregnant women. Animal reproduction studies have not been conducted with FEIBA. It is also not known whether FEIBA can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. In the U.S. general population, the estimated background risk for major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. There is no information available on the effect of FEIBA on labor and delivery.

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied FEIBA is available in single-dose vials in the following nominal dosage strengths: Nominal Strength Color Code Factor VIII Potency Range Kit NDC Sterile Water Volume 500 units Orange 350-650 units per vial 64193-426-02 10 mL 1000 units Green 700-1300 units per vial 64193-424-02 20 mL 2500 units Purple 1750-3250 units per vial 64193-425-02 50 mL The number of units of factor VIII inhibitor bypassing activity is stated on the label of each vial. FEIBA is packaged with a suitable volume (10 mL, 20 mL, or 50 mL) of Sterile Water for Injection, U.S.P., one BAXJECT II Hi-Flow Needleless Transfer Device, and one Package Insert. Not made with natural rubber latex. Storage and Handling Store at 36°F to 77°F (2°C to 25°C) Store in the original package in order to protect from light. Do not freeze. Prior to preparation and reconstitution, allow the vials of FEIBA and Sterile Water for Injection (diluent) to reach room temperature, if refrigerated.

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.