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CLINICAL NEWS |
inhibitor , with best available therapy ( BAT ) in ruxolitinib-treated patients with MF . Momelotinib failed to improve rates of splenic response ( defined as ≥35 % reduction in spleen volume ; primary endpoint ), according to results published in The Lancet Haematology . However , the investigators reported that treatment appeared to be associated with improvement in diseaserelated symptoms and red blood cell ( RBC ) transfusion – independence . |
The international , multicenter , randomized , open-label trial enrolled 156 patients from 52 clinical centers in Canada , France , Germany , Israel , Italy , Spain , the U . K ., and the U . S ., between June 19 , 2014 , and July 28 , 2016 . All participants were receiving or previously received ruxolitinib for at least 28 days and required dose adjustments for grade ≥3 hematologic toxicity or were transfusion-dependent ( defined as ≥4 units of RBCs or a hemoglobin level of < 8 g / dL |
in the 8 weeks prior to randomization ). Those with previous splenectomy , spleen irradiation , grade ≥2 peripheral neuropathy , or uncontrolled concurrent illness were excluded .
Patients were stratified by transfusion dependence ( yes vs . no ) and baseline total symptom score ( TSS ; < 18 vs . ≥18 ), then randomized 2:1 to receive momelotinib 200 mg once-daily ( n = 104 ; mean age = 66.5 years ; standard deviation [ SD ] = 8.1 years ) or BAT
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administered according to standard of care and investigator ’ s discretion ( n = 52 ; mean age = 69 years ; SD = 7.4 years ).
Most patients in the momelotinib and BAT cohorts had intermediate-2 disease ( per Dynamic International Prognostic Scoring System ; 60 % and 54 %, respectively ), had an Eastern Cooperative Oncology Group score of 1 ( 59 % and 50 %), and were treated previously for 12 or more weeks with ruxolitinib ( 72 % and 64 %).
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FEIBA [ Anti-Inhibitor Coagulant Complex ] Indications and Detailed Important Risk Information
Indications for FEIBA
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 .
Detailed Important Risk Information for FEIBA WARNING : THROMBOEMBOLIC EVENTS
• Thromboembolic events have been reported during post-marketing surveillance following infusion of FEIBA , particularly following the administration of high doses ( above 200 units per kg per day ) and / or in patients with thrombotic risk factors .
• Monitor patients receiving FEIBA for signs and symptoms of thromboembolic events .
The use of FEIBA is contraindicated in patients with :
• History of 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 )
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 .
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 .
Infusion of FEIBA should not exceed a single dose of 100 units per kg body weight and daily doses of 200 units per kg body weight . Maximum injection or infusion rate must not exceed 2 units per kg of body weight per minute . 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 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 , the variant Creutzfeldt-Jakob disease ( vCJD ) agent and , theoretically , the Creutzfeldt-Jakob disease ( CJD ) agent .
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 .
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 or antifibrinolytics have been conducted . Use of antifibrinolytics within approximately 6 to 12 hours after the administration of FEIBA is not recommended .
Please see FEIBA Brief Summary of full Prescribing Information continued on the following page .