World of Difference
programs sponsored by pharmaceutical companies , such as the Pfizer-Cipla program and the Glivec International Patient Assistance Program , are steps in the right direction . ( See SIDEBAR for more information about the programs .)
“ I would say [ the Pfizer-Cipla program ] is a first break in the clouds ,” Dr . Gopal said . “ We need to celebrate these early successes , but we have to recognize that this program alone isn ’ t yet adequate to bring high-quality care to these patients .”
According to Dr . Besa ’ s hematology colleagues in Manila , even though patient-access and discounted
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 .
CONTRAINDICATIONS
• Known anaphylactic or severe hypersensitivity reactions to FEIBA or any if its components , including factors of the kinin generating system .
• Disseminated intravascular coagulation ( DIC ).
• Acute thrombosis or embolism ( including myocardial infarction ).
WARNINGS AND PRECAUTIONS Thromboembolic Events
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 ].
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 .
Hypersensitivity Reactions
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 .
Transmission of Infectious Agents
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 in full Prescribing Information ]. 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 Baxter Healthcare Corporation , at 1-800-423-2862 ( in the U . S .) and / or to FDA Med Watch ( 1-800-FDA-1088 or www . fda . gov / medwatch ).
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 . drug programs are available in the Philippines , about 20 percent of CML patients are given hydroxyurea instead of imatinib because of cost concerns . In some cases , the patients might be connected to “ grey-market ” sources who can access generic medicines from India . “ When I was asked recently to give a talk in Manila , I realized that all the drugs I was going to talk about are not affordable there ,” he said . “ I felt very frustrated .”
Low-Hanging Fruit
© 2017 Shire US Inc ., Lexington , MA 02421 . All rights reserved . 1-800-828-2088 . SHIRE and the Shire Logo are registered trademarks of Shire Pharmaceutical Holdings Ireland Limited or its affiliates . Feiba is a registered trademark of Baxalta Incorporated , a wholly owned , indirect subsidiary of Shire plc . S27124 01 / 17
It ’ s not often that a simple-to-implement and Continued on page 121
FEIBA [ Anti-Inhibitor Coagulant Complex ] For Intravenous Use , Lyophilized Powder for Solution Brief Summary of Prescribing Information . Please see package insert for full Prescribing Information .
WARNING : THROMBOEMBOLIC EVENTS
• Thromboembolic events have been reported during post-marketing 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 .
The serious adverse reactions seen with FEIBA are hypersensitivity reactions and thromboembolic events , including stroke , pulmonary embolism and deep vein thrombosis .
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 subject 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 . 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 ). Adverse reactions were defined as adverse events that occurred ( a ) within 24 hours after being infused or ( b ) adverse events assessed related or possibly related or ( c ) adverse events for which the investigator ’ s or sponsor ’ s opinion of causality was missing or indeterminate .
Table 2 Prophylaxis Study Adverse Reactions ( ARs ) in > 5 % of Subjects
MedDRA System Organ Class
Blood And Lymphatic System Disorders
Gastrointestinal Disorders
Investigations
Musculoskeletal And Connective Tissue Disorders
Preferred Term
Number of ARs
Number of Subjects
Anemia |
2 |
2 |
5.6 |
Diarrhea |
2 |
2 |
5.6 |
Nausea |
2 |
2 |
5.6 |
Vomiting |
2 |
2 |
5.6 |
|
Hepatitis B Surface
4
Antibody Positive
|
4 |
11.1 |
Hemarthrosis |
5 |
3 |
8.3 |
Percent of Subjects ( N = 36 )
Post-Marketing Experience
Because post-marketing reporting of adverse reactions is voluntarily 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
DRUG INTERACTIONS 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 wellcontrolled studies of the combined or sequential use of FEIBA and recombinant factor VIIa or antifibrinolytics have been conducted . Use of antifibrinolytics within approximately 6 to 12 hours after the administration of FEIBA is not recommended .
ASH ’ s Global Initiatives
ASH offers a wide array of programs and services to help hematologists conquer blood diseases worldwide . These include programs that place ASH members in volunteer positions educating and training hematology personnel in the developing world , as well as programs that open U . S . -based hematology training to foreign-trained physicians . For full details about these initiatives , visit hematology . org / Global .
ASH Global Capacity-Building Showcase
The Global Capacity-Building Showcase is a new poster category at the ASH annual meeting designed to showcase research and capacity-building initiatives in low- and middleincome countries . Posters will be presented in an electronic format and will highlight existing partnerships with measurable outcomes . Posters will be available for viewing at the following times during the 2017 ASH Annual Meeting :
Saturday , December 9 : 9:00 a . m . – 7:30 p . m . Sunday , December 10 : 9:00 a . m . – 8:00 p . m . Monday , December 11 : 10:00 a . m . – 8:00 p . m .
The ASH Global Research Award
The ASH Global Research Award is designed to support future international scientific leaders , increase hematology capacity , and nurture global collaboration . The award is intended to support hematologists between completion of training and the establishment of their independent careers . It is accessible to individuals across geographical regions . For more information , visit hematology . org / Global-Research .
Visitor Training Program
The Visitor Training Program helps build hematology capacity in developing countries with the goal of improving patient care . The program provides funding for hematologists or hematology-related health-care professionals in the developing world to receive training on a specific topic or technique for up to 12 weeks . Training is carried out in the clinic or laboratory of an ASH member under the ASH member ’ s supervision and mentorship . Upon completion of training , participants return to their home institutions to implement the skills and knowledge they acquired to address the specific hematology need . For more information , visit hematology . org / Awards / Career- Training / 436 . aspx .
Latin American Training Program
The Latin American Training Program is intended to build hematology capacity in Latin America around specific priority areas for the region . The program provides funding for hematologists or hematology-related healthcare professionals in Latin America to receive training in one of the following areas : Flow Cytometry and Molecular Biology , Adult Stem Cell Transplantation , Diagnosis and Treatment of Coagulopathies , Thrombosis and Hemostasis , or Pediatric Stem Cell Transplantation . For more information , visit hematology . org / Awards / Career-Training / 3061 . aspx .
Health Volunteers Overseas
ASH partners with Health Volunteers Overseas , a non-profit organization dedicated to improving global health through education , to bring consultation and training to hospitals in the developing world . Training provided by ASH members takes the form of rounds in clinics , bedside consultations , classroom lectures , laboratory visits , and more . The objective is to develop sustainable improvement in the management of hematology patients at institutions in developing nations . For more information , visit hematology . org / HVO .
December 2017