FEIBA is an Anti-Inhibitor Coagulant Complex indicated for use in hemophilia A and B patients with inhibitors for:

{ "type": "p", "children": [], "text": "FEIBA is an Anti-Inhibitor Coagulant Complex indicated for use in hemophilia A and B patients with inhibitors for:" }

{ "type": "ul", "children": [ "Control and prevention of bleeding episodes", "Perioperative management", "Routine prophylaxis to prevent or reduce the frequency of bleeding episodes." ], "text": "" }

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.

{ "type": "p", "children": [], "text": "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." }

A guide for dosing FEIBA is provided in Table 1.

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 1: Dosing Guidelines</span> </caption> <col align="left" valign="top" width="30%"/> <col align="left" valign="top" width="20%"/> <col align="left" valign="top" width="20%"/> <col align="left" valign="top" width="30%"/> <thead> <tr class="First Last"> <th align="left" class="Lrule Rrule"></th><th align="left" class="Rrule">Dose (unit/kg)</th><th align="left" class="Rrule">Frequency of Doses (hours)</th><th align="left" class="Rrule">Duration of Therapy</th> </tr> </thead> <tbody> <tr class="Botrule First"> <td align="left" class="Lrule Rrule" colspan="4"><span class="Bold">Control and Prevention of Bleeding</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Joint Hemorrhage</td><td align="left" class="Rrule">50 – 100</td><td align="left" class="Rrule">12</td><td align="left" class="Rrule">Until pain and acute disabilities are improved.</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Mucous Membrane Bleeding</td><td align="left" class="Rrule">50 – 100</td><td align="left" class="Rrule">6</td><td align="left" class="Rrule">At least 1 day or until bleeding is resolved.</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Soft Tissue Hemorrhage<br/>(e.g., retroperitoneal bleeding)</td><td align="left" class="Rrule">100</td><td align="left" class="Rrule">12</td><td align="left" class="Rrule">Until resolution of bleed.</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Other Severe Hemorrhage<br/>(e.g., CNS bleeds)</td><td align="left" class="Rrule">100</td><td align="left" class="Rrule">6 – 12</td><td align="left" class="Rrule">Until resolution of bleed.</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="4"><span class="Bold">Perioperative Management</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Preoperative</td><td align="left" class="Rrule">50 – 100</td><td align="left" class="Rrule">One time dose</td><td align="left" class="Rrule">Immediately prior to surgery.</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Postoperative</td><td align="left" class="Rrule">50 – 100</td><td align="left" class="Rrule">6 – 12</td><td align="left" class="Rrule">Until resolution of bleed and healing are achieved.</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="4"><span class="Bold">Routine Prophylaxis</span></td> </tr> <tr class="Last"> <td align="left" class="Lrule Rrule"></td><td align="left" class="Rrule">85</td><td align="left" class="Rrule">Every other day</td><td align="left" class="Rrule"></td> </tr> </tbody> </table></div>

<div class="scrollingtable"><table class="Noautorules" width="100%"> <col align="center" valign="middle" width="50%"/> <col align="center" valign="middle" width="50%"/> <tbody class="Headless"> <tr> <td align="center"><span class="Bold">Figure A</span> <br/> <img alt="Figure A" src="/dailymed/image.cfm?name=feiba-01.jpg&amp;setid=752604e5-4ea2-44f4-83ed-1569373f6412"/></td><td align="center"><span class="Bold">Figure B</span> <br/> <img alt="Figure B" src="/dailymed/image.cfm?name=feiba-02.jpg&amp;setid=752604e5-4ea2-44f4-83ed-1569373f6412"/></td> </tr> <tr> <td align="center"><span class="Bold">Figure C</span> <br/> <img alt="Figure C" src="/dailymed/image.cfm?name=feiba-03.jpg&amp;setid=752604e5-4ea2-44f4-83ed-1569373f6412"/></td><td align="center"><span class="Bold">Figure D</span> <br/> <img alt="Figure D" src="/dailymed/image.cfm?name=feiba-04.jpg&amp;setid=752604e5-4ea2-44f4-83ed-1569373f6412"/></td> </tr> </tbody> </table></div>

For intravenous injection or intravenous infusion after reconstitution only.

<div class="scrollingtable"><table class="Noautorules" width="100%"> <col align="center" valign="middle" width="50%"/> <col align="center" valign="middle" width="50%"/> <tbody class="Headless"> <tr> <td align="center"><span class="Bold">Figure E</span> <br/> <img alt="Figure E" src="/dailymed/image.cfm?name=feiba-05.jpg&amp;setid=752604e5-4ea2-44f4-83ed-1569373f6412"/></td><td align="center"><span class="Bold">Figure F</span> <br/> <img alt="Figure F" src="/dailymed/image.cfm?name=feiba-06.jpg&amp;setid=752604e5-4ea2-44f4-83ed-1569373f6412"/></td> </tr> </tbody> </table></div>

FEIBA is available as a lyophilized powder in single-dose glass vials containing nominally 500, 1000, or 2500 units per vial.

{ "type": "p", "children": [], "text": "FEIBA is available as a lyophilized powder in single-dose glass vials containing nominally 500, 1000, or 2500 units per vial." }

{ "type": "ul", "children": [ "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)." ], "text": "" }

Thromboembolic events (including venous thrombosis, pulmonary embolism, myocardial infarction, and stroke) can occur with FEIBA, particularly following the administration of high doses (above 200 units per kg per day) and/or in patients with thrombotic risk factors [see Adverse Reactions (6)].

Patients with DIC, advanced atherosclerotic disease, crush injury, septicemia, or concomitant treatment with recombinant factor VIIa have an increased risk of developing thrombotic events due to circulating tissue factor or predisposing coagulopathy. Potential benefit of treatment with FEIBA should be weighed against the potential risk of these thromboembolic events.

Monitor patients receiving more than 100 units per kg of body weight of FEIBA for the development of DIC, acute coronary ischemia and signs and symptoms of other thromboembolic events. If clinical signs or symptoms occur, such as chest pain or pressure, shortness of breath, altered consciousness, vision, or speech, limb or abdomen swelling and/or pain, discontinue the infusion and initiate appropriate diagnostic and therapeutic measures.

The safety and efficacy of FEIBA for breakthrough bleeding in patients receiving emicizumab has not been established. Cases of thrombotic microangiopathy (TMA) were reported in a clinical trial where subjects received FEIBA as part of a treatment regimen for breakthrough bleeding following treatment with emicizumab.6 Consider the benefits and risks with FEIBA if considered required for patients receiving emicizumab prophylaxis. If treatment with FEIBA is required for patients receiving emicizumab, the hemophilia treating physician should closely monitor for signs and symptoms of TMA. In FEIBA clinical studies thrombotic microangiopathy (TMA) has not been reported.

Hypersensitivity and allergic reactions, including severe anaphylactoid reactions, can occur following the infusion of FEIBA. The symptoms include urticaria, angioedema, gastrointestinal manifestations, bronchospasm, and hypotension. These reactions can be severe and systemic (e.g., anaphylaxis with urticaria and angioedema, bronchospasm, and circulatory shock). Other infusion reactions, such as chills, pyrexia, and hypertension have also been reported. If signs and symptoms of severe allergic reactions occur, immediately discontinue administration of FEIBA and provide appropriate supportive care.

Because FEIBA is made from human plasma it may carry a risk of transmitting infectious agents, e.g., viruses, and the variant Creutzfeldt-Jakob disease (vCJD) agent, and theoretically, the Creutzfeldt-Jakob disease (CJD) agent. The risk has been minimized by screening plasma donors for prior exposure to certain viruses, by testing for the presence of certain current virus infections and by inactivating and removing certain viruses during the manufacturing process [see Description (11)]. Despite these measures, the product may still potentially transmit human pathogenic agents. There is also the possibility that unknown infectious agents may still be present.

All infections thought by a physician to have been possibly transmitted by this product should be reported by the physician or other healthcare providers to Takeda Pharmaceuticals U.S.A., Inc. at 1-877-TAKEDA-7 (1-877-825-3327) (in the U.S.) and /or to FDA Med Watch (1-800-FDA-1088 or www.fda.gov/medwatch).

FEIBA contains blood group isohemagglutinins (anti-A and anti-B). Passive transmission of antibodies to erythrocyte antigens, e.g., A, B, D, may interfere with some serological tests for red cell antibodies, such as antiglobulin test (Coombs test).

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 IX3. 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).

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 2: Prophylaxis Study Adverse Reactions (ARs) in &gt;5% of Subjects</span> </caption> <col align="left" valign="middle" width="35%"/> <col align="left" valign="middle" width="20%"/> <col align="left" valign="middle" width="20%"/> <col align="left" valign="middle" width="10%"/> <col align="left" valign="middle" width="15%"/> <thead> <tr class="First Last"> <th align="left" class="Lrule Rrule">MedDRA System Organ Class</th><th align="left" class="Rrule">Adverse Reaction</th><th align="left" class="Rrule">Number of ARs</th><th align="left" class="Rrule">Number of Subjects</th><th align="left" class="Rrule">Percent of Subjects (N=36)</th> </tr> </thead> <tbody> <tr class="Botrule First"> <td align="left" class="Lrule Rrule"><span class="Bold">Blood And Lymphatic System Disorders</span></td><td align="left" class="Rrule">Anemia</td><td align="left" class="Rrule">2</td><td align="left" class="Rrule">2</td><td align="left" class="Rrule">5.6</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" rowspan="3" valign="top"><span class="Bold">Gastrointestinal Disorders</span></td><td align="left" class="Rrule">Diarrhea</td><td align="left" class="Rrule">2</td><td align="left" class="Rrule">2</td><td align="left" class="Rrule">5.6</td> </tr> <tr class="Botrule"> <td align="left" class="Rrule">Nausea</td><td align="left" class="Rrule">2</td><td align="left" class="Rrule">2</td><td align="left" class="Rrule">5.6</td> </tr> <tr class="Botrule"> <td align="left" class="Rrule">Vomiting</td><td align="left" class="Rrule">2</td><td align="left" class="Rrule">2</td><td align="left" class="Rrule">5.6</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule"><span class="Bold">Investigations</span></td><td align="left" class="Rrule">Hepatitis B Surface Antibody Positive</td><td align="left" class="Rrule">4</td><td align="left" class="Rrule">4</td><td align="left" class="Rrule">11.1</td> </tr> <tr class="Last"> <td align="left" class="Lrule Rrule"><span class="Bold">Musculoskeletal And Connective Tissue Disorders</span></td><td align="left" class="Rrule">Hemarthrosis</td><td align="left" class="Rrule">5</td><td align="left" class="Rrule">3</td><td align="left" class="Rrule">8.3</td> </tr> </tbody> </table></div>

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 the randomized, prospective crossover trial evaluating the tolerability and safety of infusing reduced volume of FEIBA at the standard infusion rate of 2 U/kg/min, and at increased rates of 4 and 10 U/kg/min in a total of 33 treated subjects with congenital Hemophilia A with inhibitors.

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 3: Adverse Reactions (ARs) and Infusion Related Adverse Events in &gt;5% of Subjects, in Patients 18 Years and Older</span> </caption> <col align="left" valign="middle" width="18%"/> <col align="left" valign="middle" width="17%"/> <col align="center" valign="middle" width="11%"/> <col align="center" valign="middle" width="18%"/> <col align="center" valign="middle" width="18%"/> <col align="center" valign="middle" width="18%"/> <thead> <tr class="First Last"> <th align="left" class="Lrule Rrule"></th><th align="left" class="Rrule">MedDRA System Organ Class </th><th align="center" class="Rrule">Adverse Reaction</th><th align="center" class="Rrule">50% Reduced Volume; Increased Rate 4 U/kg/min<br/>(N=30)<br/>n (%); m<br/> </th><th align="center" class="Rrule">50% Reduced Volume; Increased Rate 10 U/kg/min<br/>(N=28)<br/>n (%); m<br/> </th><th align="center" class="Rrule">Overall<br/>50% Reduced Volume<a class="Sup" href="#footnote-1" name="footnote-reference-1">*</a> <br/>(N=30)<br/>n (%); m<br/> </th> </tr> </thead> <tfoot> <tr class="First Last"> <td align="left" colspan="6">n=Number of subjects, m=number of events</td> </tr> <tr> <td align="left" colspan="6"> <dl class="Footnote"> <dt> <a href="#footnote-reference-1" name="footnote-1">*</a> </dt> <dd>Includes the following infusion rates: 2 U/kg/min; 4 U/kg/min and 10 U/kg/min</dd> </dl> </td> </tr> </tfoot> <tbody> <tr class="Botrule First"> <td align="left" class="Lrule Rrule">Adverse reactions (ARs)</td><td align="left" class="Rrule">Nervous system disorders</td><td align="center" class="Rrule">Headache</td><td align="center" class="Rrule">0</td><td align="center" class="Rrule">0</td><td align="center" class="Rrule">2 (6.7%); 2</td> </tr> <tr class="Botrule Last"> <td align="left" class="Lrule Rrule">Infusion related AEs</td><td align="left" class="Rrule">Nervous system disorders</td><td align="center" class="Rrule">Headache</td><td align="center" class="Rrule">0</td><td align="center" class="Rrule">0</td><td align="center" class="Rrule">2 (6.7%); 2</td> </tr> </tbody> </table></div>

The following adverse reactions have been identified during post-approval use of FEIBA. Because postmarketing reporting of adverse reactions is voluntary and from a population of uncertain size, it is not always possible to reliably estimate the frequency of these reactions or establish a causal relationship to product exposure.

Blood and Lymphatic System Disorders: disseminated intravascular coagulation

Cardiac Disorders: tachycardia, flushing

Respiratory, Thoracic, and Mediastinal Disorders: bronchospasm, wheezing

Gastrointestinal Disorders: abdominal discomfort

Skin and Subcutaneous Tissue Disorders: pruritus

General Disorders and Administration Site Conditions: malaise, feeling hot, injection site pain

Investigations: Fibrin D-dimer increased

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 bleeding6 [see Warnings and Precautions (5.1)].

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.

Risk Summary

There is no information regarding the presence of FEIBA in human milk, the effect on the breastfed child, or the effects on milk production.

The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for FEIBA and any potential adverse effects on the breastfed child from FEIBA or from the underlying condition.

Safety and efficacy of FEIBA have been evaluated in nine pediatric subjects treated in the routine prophylaxis trial including 4 subjects ≥7 to <12 years of age and 5 subjects ≥12 to <16 years of age. The dosing for all pediatric subjects was based on body weight. A total of 576 infusions were given for the treatment of 223 bleeding episodes (504 infusions for joint bleeding episodes, 72 infusions for muscle and soft tissue bleeding episodes). In 223 (100%) of the episodes, hemostasis was achieved with one or more infusions. Hemostatic efficacy was rated as excellent or good in a majority (96.9%) of the bleeding episodes in both regimens at 24 hours post infusion. The median annualized bleeding episode rate (ABR) for children ≥7 to <12 years of age was 7.7 bleeds per patient per year, as compared to 39 for subjects treated with on-demand therapy [see Clinical Studies (14)].

The safety and efficacy of FEIBA has not been evaluated in neonates.

The safety and efficacy of FEIBA has not been evaluated in subjects ≥65 years of age.

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.

{ "type": "p", "children": [], "text": "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.

{ "type": "p", "children": [], "text": "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).

{ "type": "p", "children": [], "text": "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.

{ "type": "p", "children": [], "text": "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 viruses. Table 4 summarizes the results of the viral clearance studies for FEIBA.

{ "type": "p", "children": [], "text": "\nIn vitro spiking studies have been used to validate the capability of the manufacturing process to remove and inactivate viruses. Table 4 summarizes the results of the viral clearance studies for FEIBA." }

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 4: Virus Reduction Factors (log<span class="Sub">10</span>) During Manufacturing FEIBA</span> </caption> <col align="left" valign="middle" width="18%"/> <col align="left" valign="middle" width="16%"/> <col align="left" valign="middle" width="8%"/> <col align="left" valign="middle" width="8%"/> <col align="left" valign="middle" width="15%"/> <col align="left" valign="middle" width="15%"/> <col align="left" valign="middle" width="10%"/> <col align="left" valign="middle" width="10%"/> <thead> <tr class="Botrule First"> <th align="left" class="Lrule Rrule">Virus Type</th><th align="left" class="Rrule" colspan="3">Enveloped RNA</th><th align="left" class="Rrule">Enveloped DNA</th><th align="left" class="Rrule">Non-enveloped RNA</th><th align="left" class="Rrule" colspan="2">Non-enveloped DNA</th> </tr> <tr class="Botrule Last"> <th align="left" class="Lrule Rrule">Virus Family</th><th align="left" class="Rrule">Retroviridae</th><th align="left" class="Rrule" colspan="2">Flaviviridae</th><th align="left" class="Rrule">Herpesviridae</th><th align="left" class="Rrule">Picornaviridae</th><th align="left" class="Rrule" colspan="2">Parvoviridae</th> </tr> </thead> <tfoot> <tr> <td align="left" colspan="8"> <dl class="Footnote"> <dt> <a href="#footnote-reference-2" name="footnote-2">*</a> </dt> <dd>Abbreviations: HIV-1, Human Immunodeficiency Virus Type 1; BVDV, Bovine Viral Diarrhea Virus (model for Hepatitis C Virus and other lipid enveloped RNA viruses); WNV, West Nile Virus; PRV, Pseudo rabies Virus (model for lipid enveloped DNA viruses, including Hepatitis B Virus); HAV, Hepatitis A Virus; MMV, Mice Minute Virus (model for non-lipid enveloped DNA viruses, including B19 virus [B19V]). ND not done</dd> <dt> <a href="#footnote-reference-3" name="footnote-3">†</a> </dt> <dd>Reduction factor for Parvovirus B19 claimed for the Vapor Heat Treatment is based on results derived from experimental infectivity and titration assays.</dd> <dt> <a href="#footnote-reference-4" name="footnote-4">‡</a> </dt> <dd>Reduction factors &lt;1 log are not used for calculation of the overall reduction factor.</dd> </dl> </td> </tr> </tfoot> <tbody> <tr class="Botrule First"> <td align="left" class="Lrule Rrule">Virus<a class="Sup" href="#footnote-2" name="footnote-reference-2">*</a></td><td align="left" class="Rrule">HIV-1</td><td align="left" class="Rrule">BVDV</td><td align="left" class="Rrule">WNV</td><td align="left" class="Rrule">PRV</td><td align="left" class="Rrule">HAV</td><td align="left" class="Rrule">B19V<a class="Sup" href="#footnote-3" name="footnote-reference-3">†</a></td><td align="left" class="Rrule">MMV</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">DEAE Sephadex Adsorption</td><td align="left" class="Rrule">3.2</td><td align="left" class="Rrule">1.8</td><td align="left" class="Rrule">ND</td><td align="left" class="Rrule">2.5</td><td align="left" class="Rrule">1.5</td><td align="left" class="Rrule">1.7</td><td align="left" class="Rrule">1.2</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">35 nm Nanofiltration</td><td align="left" class="Rrule">&gt;5.3</td><td align="left" class="Rrule">2.1</td><td align="left" class="Rrule">4.7</td><td align="left" class="Rrule">&gt;5.7</td><td align="left" class="Rrule">2.6</td><td align="left" class="Rrule">0.2<a class="Sup" href="#footnote-4" name="footnote-reference-4">‡</a></td><td align="left" class="Rrule">1.0</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Vapor-Heat Treatment</td><td align="left" class="Rrule">&gt;5.9</td><td align="left" class="Rrule">&gt;5.6</td><td align="left" class="Rrule">&gt;8.1</td><td align="left" class="Rrule">&gt;6.7</td><td align="left" class="Rrule">&gt;5.2</td><td align="left" class="Rrule">3.5</td><td align="left" class="Rrule">0.9<a class="Sup" href="#footnote-4">‡</a></td> </tr> <tr class="Last"> <td align="left" class="Lrule Rrule">Overall virus reduction factor (log10)</td><td align="left" class="Rrule">&gt;14.4</td><td align="left" class="Rrule">&gt;9.5</td><td align="left" class="Rrule">&gt;12.8</td><td align="left" class="Rrule">&gt;14.9</td><td align="left" class="Rrule">&gt;9.3</td><td align="left" class="Rrule">5.2</td><td align="left" class="Rrule">2.2</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"100%\">\n<caption>\n<span>Table 4: Virus Reduction Factors (log<span class=\"Sub\">10</span>) During Manufacturing FEIBA</span>\n</caption>\n<col align=\"left\" valign=\"middle\" width=\"18%\"/>\n<col align=\"left\" valign=\"middle\" width=\"16%\"/>\n<col align=\"left\" valign=\"middle\" width=\"8%\"/>\n<col align=\"left\" valign=\"middle\" width=\"8%\"/>\n<col align=\"left\" valign=\"middle\" width=\"15%\"/>\n<col align=\"left\" valign=\"middle\" width=\"15%\"/>\n<col align=\"left\" valign=\"middle\" width=\"10%\"/>\n<col align=\"left\" valign=\"middle\" width=\"10%\"/>\n<thead>\n<tr class=\"Botrule First\">\n<th align=\"left\" class=\"Lrule Rrule\">Virus Type</th><th align=\"left\" class=\"Rrule\" colspan=\"3\">Enveloped RNA</th><th align=\"left\" class=\"Rrule\">Enveloped DNA</th><th align=\"left\" class=\"Rrule\">Non-enveloped RNA</th><th align=\"left\" class=\"Rrule\" colspan=\"2\">Non-enveloped DNA</th>\n</tr>\n<tr class=\"Botrule Last\">\n<th align=\"left\" class=\"Lrule Rrule\">Virus Family</th><th align=\"left\" class=\"Rrule\">Retroviridae</th><th align=\"left\" class=\"Rrule\" colspan=\"2\">Flaviviridae</th><th align=\"left\" class=\"Rrule\">Herpesviridae</th><th align=\"left\" class=\"Rrule\">Picornaviridae</th><th align=\"left\" class=\"Rrule\" colspan=\"2\">Parvoviridae</th>\n</tr>\n</thead>\n<tfoot>\n<tr>\n<td align=\"left\" colspan=\"8\">\n<dl class=\"Footnote\">\n<dt>\n<a href=\"#footnote-reference-2\" name=\"footnote-2\">*</a>\n</dt>\n<dd>Abbreviations: HIV-1, Human Immunodeficiency Virus Type 1; BVDV, Bovine Viral Diarrhea Virus (model for Hepatitis C Virus and other lipid enveloped RNA viruses); WNV, West Nile Virus; PRV, Pseudo rabies Virus (model for lipid enveloped DNA viruses, including Hepatitis B Virus); HAV, Hepatitis A Virus; MMV, Mice Minute Virus (model for non-lipid enveloped DNA viruses, including B19 virus [B19V]). ND not done</dd>\n<dt>\n<a href=\"#footnote-reference-3\" name=\"footnote-3\">†</a>\n</dt>\n<dd>Reduction factor for Parvovirus B19 claimed for the Vapor Heat Treatment is based on results derived from experimental infectivity and titration assays.</dd>\n<dt>\n<a href=\"#footnote-reference-4\" name=\"footnote-4\">‡</a>\n</dt>\n<dd>Reduction factors &lt;1 log are not used for calculation of the overall reduction factor.</dd>\n</dl>\n</td>\n</tr>\n</tfoot>\n<tbody>\n<tr class=\"Botrule First\">\n<td align=\"left\" class=\"Lrule Rrule\">Virus<a class=\"Sup\" href=\"#footnote-2\" name=\"footnote-reference-2\">*</a></td><td align=\"left\" class=\"Rrule\">HIV-1</td><td align=\"left\" class=\"Rrule\">BVDV</td><td align=\"left\" class=\"Rrule\">WNV</td><td align=\"left\" class=\"Rrule\">PRV</td><td align=\"left\" class=\"Rrule\">HAV</td><td align=\"left\" class=\"Rrule\">B19V<a class=\"Sup\" href=\"#footnote-3\" name=\"footnote-reference-3\">†</a></td><td align=\"left\" class=\"Rrule\">MMV</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\">DEAE Sephadex Adsorption</td><td align=\"left\" class=\"Rrule\">3.2</td><td align=\"left\" class=\"Rrule\">1.8</td><td align=\"left\" class=\"Rrule\">ND</td><td align=\"left\" class=\"Rrule\">2.5</td><td align=\"left\" class=\"Rrule\">1.5</td><td align=\"left\" class=\"Rrule\">1.7</td><td align=\"left\" class=\"Rrule\">1.2</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\">35 nm Nanofiltration</td><td align=\"left\" class=\"Rrule\">&gt;5.3</td><td align=\"left\" class=\"Rrule\">2.1</td><td align=\"left\" class=\"Rrule\">4.7</td><td align=\"left\" class=\"Rrule\">&gt;5.7</td><td align=\"left\" class=\"Rrule\">2.6</td><td align=\"left\" class=\"Rrule\">0.2<a class=\"Sup\" href=\"#footnote-4\" name=\"footnote-reference-4\">‡</a></td><td align=\"left\" class=\"Rrule\">1.0</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\">Vapor-Heat Treatment</td><td align=\"left\" class=\"Rrule\">&gt;5.9</td><td align=\"left\" class=\"Rrule\">&gt;5.6</td><td align=\"left\" class=\"Rrule\">&gt;8.1</td><td align=\"left\" class=\"Rrule\">&gt;6.7</td><td align=\"left\" class=\"Rrule\">&gt;5.2</td><td align=\"left\" class=\"Rrule\">3.5</td><td align=\"left\" class=\"Rrule\">0.9<a class=\"Sup\" href=\"#footnote-4\">‡</a></td>\n</tr>\n<tr class=\"Last\">\n<td align=\"left\" class=\"Lrule Rrule\">Overall virus reduction factor (log10)</td><td align=\"left\" class=\"Rrule\">&gt;14.4</td><td align=\"left\" class=\"Rrule\">&gt;9.5</td><td align=\"left\" class=\"Rrule\">&gt;12.8</td><td align=\"left\" class=\"Rrule\">&gt;14.9</td><td align=\"left\" class=\"Rrule\">&gt;9.3</td><td align=\"left\" class=\"Rrule\">5.2</td><td align=\"left\" class=\"Rrule\">2.2</td>\n</tr>\n</tbody>\n</table></div>" }

The mechanism of action of FEIBA is still the subject of scientific discussion. FEIBA contains multiple components, mainly non-activated factors II, IX, X and mainly activated factor VII. These factors can interact with plasma coagulation factors and platelets to increase the impaired thrombin generation of hemophilia patients with inhibitors, leading to hemostasis.

Laboratory assessment of coagulation does not necessarily correlate with or predict the hemostatic effectiveness of FEIBA. Factor VIII inhibitor bypassing activity of FEIBA has been demonstrated in vitro as well as in vivo. FEIBA can shorten the activated partial thromboplastin time (aPTT) and increase the thrombin generation in plasma containing factor VIII inhibitor.4,5

FEIBA is composed of different coagulation factors, with varying half-lives for the individual components. The pharmacokinetic properties of FEIBA have not been formally studied in humans.

Long-term animal studies to evaluate the carcinogenic potential of FEIBA or studies to determine the genotoxicity or the effect of FEIBA on fertility have not been performed. An assessment of the carcinogenic potential of FEIBA was completed to demonstrate minimal carcinogenic risk from product use.

Control and Prevention of Bleeding Episodes

{ "type": "p", "children": [], "text": "\nControl and Prevention of Bleeding Episodes\n" }

The efficacy of FEIBA in the treatment of bleeding episodes has been demonstrated by two prospective clinical trials.1,2

{ "type": "p", "children": [], "text": "The efficacy of FEIBA in the treatment of bleeding episodes has been demonstrated by two prospective clinical trials.1,2\n" }

The first trial was a multicenter, randomized, double-blind trial comparing the effect of FEIBA and a non-activated prothrombin complex concentrate in 15 subjects with hemophilia A and inhibitors to factor VIII. The inclusion criteria were history of high titer inhibitors, high responder status, more than 1 bleeding episode per month in the prior year and no signs of liver failure. A total of 150 bleeding episodes including 117 joint, 20 musculoskeletal and 4 mucocutaneous bleeds, were treated. A single dose of 88 units per kg of body weight 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.

{ "type": "p", "children": [], "text": "The first trial was a multicenter, randomized, double-blind trial comparing the effect of FEIBA and a non-activated prothrombin complex concentrate in 15 subjects with hemophilia A and inhibitors to factor VIII. The inclusion criteria were history of high titer inhibitors, high responder status, more than 1 bleeding episode per month in the prior year and no signs of liver failure. A total of 150 bleeding episodes including 117 joint, 20 musculoskeletal and 4 mucocutaneous bleeds, were treated. A single dose of 88 units per kg of body weight 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." }

Subjects 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 (i.e. combined effectiveness of 66%), while prothrombin complex concentrate was rated effective in 25% and partly effective in 21% of episodes (i.e., combined effectiveness of 46%).

{ "type": "p", "children": [], "text": "Subjects 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 (i.e. combined effectiveness of 66%), while prothrombin complex concentrate was rated effective in 25% and partly effective in 21% of episodes (i.e., combined effectiveness of 46%)." }

The second trial with FEIBA was a multicenter randomized, prospective trial. This trial was conducted in 44 hemophilia A subjects with inhibitors, 3 hemophilia B subjects with inhibitors and 2 acquired factor VIII inhibitor subjects. 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. The inclusion criteria used were age >4 years, history of inhibitor titer ≥4 Bethesda Units (BU) and without chronic liver disease. Subjects were excluded if they had a history of thromboembolic events or allergic reactions to FEIBA.

{ "type": "p", "children": [], "text": "The second trial with FEIBA was a multicenter randomized, prospective trial. This trial was conducted in 44 hemophilia A subjects with inhibitors, 3 hemophilia B subjects with inhibitors and 2 acquired factor VIII inhibitor subjects. 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. The inclusion criteria used were age >4 years, history of inhibitor titer ≥4 Bethesda Units (BU) and without chronic liver disease. Subjects were excluded if they had a history of thromboembolic events or allergic reactions to FEIBA." }

Forty-nine (49) subjects with inhibitor titers of greater than 5 BU were enrolled from nine co-operating hemophilia centers. Subjects were treated with 50 units per kg of body weight, 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 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.

{ "type": "p", "children": [], "text": "Forty-nine (49) subjects with inhibitor titers of greater than 5 BU were enrolled from nine co-operating hemophilia centers. Subjects were treated with 50 units per kg of body weight, 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 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." }

Routine Prophylaxis

{ "type": "p", "children": [], "text": "\nRoutine Prophylaxis\n" }

In a multicenter, open-label, prospective, randomized clinical trial comparing subjects receiving FEIBA for prophylaxis with subjects receiving FEIBA for on-demand treatment, 36 hemophilia A and B subjects with inhibitors to factor VIII or IX were analyzed in the intent-to-treat analysis. Study population included 29 (80.6%) Caucasian, 3 (8.3%) Asian, 2 (5.6%) Black/African American, and 2 (5.6%) other. Inclusion criteria were subjects with a history of high titer inhibitors or low titer refractory to increased factor VIII or IX dosing, age range between 4 and 65, and subjects receiving bypassing agents with ≥12 bleeds in the 12 months prior to trial entry. Subjects with a history of thromboembolic events, symptomatic liver disease, or a platelet count <100,000 per mL, and those receiving immune tolerance induction or routine prophylaxis were excluded.

{ "type": "p", "children": [], "text": "In a multicenter, open-label, prospective, randomized clinical trial comparing subjects receiving FEIBA for prophylaxis with subjects receiving FEIBA for on-demand treatment, 36 hemophilia A and B subjects with inhibitors to factor VIII or IX were analyzed in the intent-to-treat analysis. Study population included 29 (80.6%) Caucasian, 3 (8.3%) Asian, 2 (5.6%) Black/African American, and 2 (5.6%) other. Inclusion criteria were subjects with a history of high titer inhibitors or low titer refractory to increased factor VIII or IX dosing, age range between 4 and 65, and subjects receiving bypassing agents with ≥12 bleeds in the 12 months prior to trial entry. Subjects with a history of thromboembolic events, symptomatic liver disease, or a platelet count <100,000 per mL, and those receiving immune tolerance induction or routine prophylaxis were excluded." }

Subjects were randomized to receive 12 months of prophylactic or on-demand treatment with FEIBA. Seventeen subjects randomized to the prophylaxis arm received 85 units per kg of FEIBA every other day. Nineteen subjects 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.

{ "type": "p", "children": [], "text": "Subjects were randomized to receive 12 months of prophylactic or on-demand treatment with FEIBA. Seventeen subjects randomized to the prophylaxis arm received 85 units per kg of FEIBA every other day. Nineteen subjects 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.

{ "type": "p", "children": [], "text": "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 hour 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.

{ "type": "p", "children": [], "text": "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 hour 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 subjects who received on-demand therapy.

{ "type": "p", "children": [], "text": "Hemostatic efficacy for routine prophylaxis was evaluated against subjects 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 (e.g. joint, non-joint) and cause of bleed (e.g. spontaneous, traumatic), prophylactic treatment with FEIBA resulted in a greater than 50% reduction in ABR. There were fewer subjects in the prophylaxis arm who developed new target joints (7 new target joints in 5 subjects treated with prophylaxis compared to 23 new target joints in 11 subjects in the on-demand arm). Target joints developed in two subjects in the on-demand arm and three in the prophylaxis arm who did not have reported target joints at trial enrollment. A total of 3 of 17 (18%) subjects had no bleeding episodes on prophylaxis. In the on-demand arm, all subjects experienced a bleeding episode.

{ "type": "p", "children": [], "text": "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 (e.g. joint, non-joint) and cause of bleed (e.g. spontaneous, traumatic), prophylactic treatment with FEIBA resulted in a greater than 50% reduction in ABR. There were fewer subjects in the prophylaxis arm who developed new target joints (7 new target joints in 5 subjects treated with prophylaxis compared to 23 new target joints in 11 subjects in the on-demand arm). Target joints developed in two subjects in the on-demand arm and three in the prophylaxis arm who did not have reported target joints at trial enrollment. A total of 3 of 17 (18%) subjects had no bleeding episodes on prophylaxis. In the on-demand arm, all subjects experienced a bleeding episode." }

ABR by age category between on-demand and prophylaxis regimens is provided in Table 5. One adolescent subject on prophylaxis had a higher rate of bleeding possibly due to increased physical activity after study enrollment.

{ "type": "p", "children": [], "text": "ABR by age category between on-demand and prophylaxis regimens is provided in Table 5. One adolescent subject on prophylaxis had a higher rate of bleeding possibly due to increased physical activity after study enrollment." }

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 5: ABR by Age Category</span> </caption> <col align="left" valign="middle" width="19%"/> <col align="center" valign="middle" width="18%"/> <col align="center" valign="middle" width="15%"/> <col align="center" valign="middle" width="24%"/> <col align="center" valign="middle" width="24%"/> <thead> <tr class="Botrule First Last"> <th align="left" class="Lrule Rrule">Age Category</th><th align="center" class="Lrule Rrule">On-Demand: <br/>Number of Subjects</th><th align="center" class="Lrule Rrule">On-Demand: <br/>ABR Median</th><th align="center" class="Lrule Rrule">Prophylaxis: <br/>Number of Subjects</th><th align="center" class="Lrule Rrule">Prophylaxis: <br/>ABR Median</th> </tr> </thead> <tbody> <tr class="Botrule First"> <td align="left" class="Lrule Rrule">Children<br/>(≥7 to &lt;12 years old)</td><td align="center" class="Rrule">2</td><td align="center" class="Rrule">39.3</td><td align="center" class="Rrule">2</td><td align="center" class="Rrule">7.7</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Adolescent<br/>(≥12 to &lt;16 years old)</td><td align="center" class="Rrule">2</td><td align="center" class="Rrule">30.9</td><td align="center" class="Rrule">3</td><td align="center" class="Rrule">27.5</td> </tr> <tr class="Last"> <td align="left" class="Lrule Rrule">Adult<br/>(≥16 years old)</td><td align="center" class="Rrule">15</td><td align="center" class="Rrule">23.9</td><td align="center" class="Rrule">12</td><td align="center" class="Rrule">6.9</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"100%\">\n<caption>\n<span>Table 5: ABR by Age Category</span>\n</caption>\n<col align=\"left\" valign=\"middle\" width=\"19%\"/>\n<col align=\"center\" valign=\"middle\" width=\"18%\"/>\n<col align=\"center\" valign=\"middle\" width=\"15%\"/>\n<col align=\"center\" valign=\"middle\" width=\"24%\"/>\n<col align=\"center\" valign=\"middle\" width=\"24%\"/>\n<thead>\n<tr class=\"Botrule First Last\">\n<th align=\"left\" class=\"Lrule Rrule\">Age Category</th><th align=\"center\" class=\"Lrule Rrule\">On-Demand: <br/>Number of Subjects</th><th align=\"center\" class=\"Lrule Rrule\">On-Demand: <br/>ABR Median</th><th align=\"center\" class=\"Lrule Rrule\">Prophylaxis: <br/>Number of Subjects</th><th align=\"center\" class=\"Lrule Rrule\">Prophylaxis: <br/>ABR Median</th>\n</tr>\n</thead>\n<tbody>\n<tr class=\"Botrule First\">\n<td align=\"left\" class=\"Lrule Rrule\">Children<br/>(≥7 to &lt;12 years old)</td><td align=\"center\" class=\"Rrule\">2</td><td align=\"center\" class=\"Rrule\">39.3</td><td align=\"center\" class=\"Rrule\">2</td><td align=\"center\" class=\"Rrule\">7.7</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\">Adolescent<br/>(≥12 to &lt;16 years old)</td><td align=\"center\" class=\"Rrule\">2</td><td align=\"center\" class=\"Rrule\">30.9</td><td align=\"center\" class=\"Rrule\">3</td><td align=\"center\" class=\"Rrule\">27.5</td>\n</tr>\n<tr class=\"Last\">\n<td align=\"left\" class=\"Lrule Rrule\">Adult<br/>(≥16 years old)</td><td align=\"center\" class=\"Rrule\">15</td><td align=\"center\" class=\"Rrule\">23.9</td><td align=\"center\" class=\"Rrule\">12</td><td align=\"center\" class=\"Rrule\">6.9</td>\n</tr>\n</tbody>\n</table></div>" }

{ "type": "", "children": [], "text": "" }

How Supplied

FEIBA is available in single-dose vials in the following nominal dosage strengths:

<div class="scrollingtable"><table width="100%"> <col align="left" valign="middle" width="18%"/> <col align="left" valign="middle" width="14%"/> <col align="left" valign="middle" width="25%"/> <col align="left" valign="middle" width="18%"/> <col align="left" valign="middle" width="25%"/> <thead> <tr class="First Last"> <th align="left" class="Lrule Rrule">Nominal Strength</th><th align="left" class="Rrule">Color Code</th><th align="left" class="Rrule">Factor VIII Potency Range</th><th align="left" class="Rrule">Kit NDC</th><th align="left" class="Rrule">Sterile Water Volume</th> </tr> </thead> <tbody> <tr class="Botrule First"> <td align="left" class="Lrule Rrule"><span class="Bold">500 units</span></td><td align="left" class="Rrule">Orange</td><td align="left" class="Rrule">350-650 units per vial</td><td align="left" class="Rrule">64193-426-02</td><td align="left" class="Rrule">10 mL</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule"><span class="Bold">1000 units</span></td><td align="left" class="Rrule">Green</td><td align="left" class="Rrule">700-1300 units per vial</td><td align="left" class="Rrule">64193-424-02</td><td align="left" class="Rrule">20 mL</td> </tr> <tr class="Last"> <td align="left" class="Lrule Rrule"><span class="Bold">2500 units</span></td><td align="left" class="Rrule">Purple</td><td align="left" class="Rrule">1750-3250 units per vial</td><td align="left" class="Rrule">64193-425-02</td><td align="left" class="Rrule">50 mL</td> </tr> </tbody> </table></div>

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

Inform patients:

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{ "type": "ul", "children": [ "of the signs and symptoms of thrombosis, such as chest pain or pressure, shortness of breath, altered consciousness, vision, or speech, limb or abdomen swelling and/or pain. Advise patients to seek immediate medical attention if any of these symptoms occur.", "of the signs and symptoms of hypersensitivity reactions, such as urticaria, angioedema, gastrointestinal manifestations, bronchospasm, and hypotension. Advise patients to discontinue use of the product if these symptoms occur and seek immediate emergency treatment.", "that because FEIBA is made from human blood, it may carry a risk of transmitting infectious agents, e.g., viruses, the variant Creutzfeldt-Jakob disease (vCJD) agent, and theoretically, the Creutzfeldt-Jakob disease (CJD) agent.", "if they are on emicizumab prophylaxis therapy and need FEIBA to treat a breakthrough bleeding episode then they must be monitored by their hemophilia treating physician, preferably at the hemophilia treatment center (HTC).", "to report any adverse reactions or problems following FEIBA administration to their hemophilia treating physician." ], "text": "" }

To enroll in the confidential, Industry-wide Patient Notification System, call 1-888-873-2838.

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Takeda Pharmaceuticals U.S.A., Inc. Cambridge, MA 02142 U.S. License No. 1898

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FEIBA is a registered trademark of Baxalta Incorporated.

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Takeda and are registered trademarks of Takeda Pharmaceutical Company Limited.

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©2024 Takeda Pharmaceutical Company Limited. All rights reserved.

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20 mL size, driedNDC 64193-424-02

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Anti-Inhibitor Coagulant ComplexFEIBA

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Nanofiltered & Vapor Heated

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For Intravenous Use After Reconstitution Contains no preservative

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Dosage and Administration: See accompanying package insert.

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Storage: 36°F to 77°F (2°C to 25°C). Store in the original package in order to protect from light.

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Reconstitution: Use 20 mL sWFI, U.S.P.;Do not refrigerate after reconstitution.; Use within 3 hours ofreconstitution.

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Do Not Freeze

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Rx Only

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Takeda

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Includes BAXJECT II Hi-FlowNeedleless Transfer Device

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20 mL size, driedNDC 64193-324-01

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Anti-Inhibitor Coagulant ComplexFEIBANanofiltered & Vapor Heated

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For Intravenous Use After ReconstitutionContains no preservative

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Dosage & Administration: See accompanying package insert.

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Storage: 36°F to 77°F (2°C to 25°C).

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Reconstitution: Use 20 mL sWFI, U.S.P.; Do not refrigerateafter reconstitution.; Use within 3 hours of reconstitution.

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Rx only0754401

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Single-dose vial NDC 64193-425-02

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Anti-Inhibitor Coagulant ComplexFEIBA

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Nanofiltered & Vapor Heated

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For Intravenous Use After Reconstitution Contains no preservative

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Dosage and Administration: See accompanying package insert.

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Storage: 36°F to 77°F (2°C to 25°C).Store in the original package in order to protect from light.

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Reconstitution: Use 50 mL sWFI, U.S.P.; Do not refrigerate after reconstitution.; Use within 3 hours ofreconstitution.

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Do Not Freeze

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Rx Only

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Takeda

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Includes BAXJECT II Hi-FlowNeedleless Transfer Device

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50 mL size, driedNDC 64193-325-01

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Anti-Inhibitor Coagulant ComplexFEIBANanofiltered & Vapor Heated

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For Intravenous Use After ReconstitutionContains no preservative

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Dosage & Administration: See accompanying package insert.

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Storage: 36°F to 77°F (2°C to 25°C).

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Reconstitution: Use 50 mL sWFI, U.S.P.; Do not refrigerateafter reconstitution.; Use within 3 hours of reconstitution.

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Rx only0754404

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Single-dose vialNDC 64193-426-02

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Anti-InhibitorCoagulant ComplexFEIBA

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Nanofiltered & Vapor Heated

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For Intravenous Use After Reconstitution Contains no preservative

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Dosage and Administration: See accompanying package insert.

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Storage: 36°F to 77°F (2°C to 25°C). Store in the original package in order to protectfrom light.

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Reconstitution: Use 10 mL sWFI, U.S.P.; Do not refrigerate after reconstitution.; Use within3 hours of reconstitution.

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Do Not Freeze

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Rx Only

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Takeda

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Includes BAXJECT II Hi-FlowNeedleless Transfer Device

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Single-dose vialNDC 64193-326-01

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Anti-Inhibitor Coagulant ComplexFEIBANanofiltered & Vapor Heated

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For Intravenous Use After ReconstitutionNo preservative

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Dosage & Administration: See accompanying package insert.

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Storage: 36°F to 77°F (2°C to 25°C).

{ "type": "p", "children": [], "text": "Storage: 36°F to 77°F (2°C to 25°C)." }

Reconstitution: Use 10 mL sWFI, U.S.P.; Do not refrigerate afterreconstitution.; Use within 3 hours of reconstitution.

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Rx onlyTakeda0754406

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