Feiba Warnings

Hypersensitivity Reactions: FEIBA can precipitate allergic-type hypersensitivity reactions that have included, urticaria, angioedema, gastrointestinal manifestations, bronchospasm, and hypotension; these reactions can be severe and can be 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.
Patients should be informed of the early signs of hypersensitivity reactions, for example erythema, skin rash, generalized urticaria, pruritus, breathing difficulties/dyspnea, tightness of the chest, general indisposition, dizziness and drop in blood pressure up to allergic shock.
At the first sign or symptom of an infusion/hypersensitivity reaction, FEIBA administration should be stopped and medical care initiated as appropriate.
When considering re-exposure to FEIBA in patients with suspected hypersensitivity to the product or any of its components, the expected benefit and the risk of re-exposure must be carefully weighed, taking into account the known or suspected type of the patient's hypersensitivity (allergic or non-allergic), including potential remedial and/or preventative therapy or alternative therapeutic agents.
Thrombotic and Thromboembolic Events: Thrombotic and thromboembolic events, including disseminated intravascular coagulation (DIC), venous thrombosis, pulmonary embolism, myocardial infarction, and stroke, have occurred in the course of treatment with FEIBA.
Some of these events occurred with doses above 200 U/kg/day or in patients with other risk factors (including DIC, advanced atherosclerotic disease, crush injury or septicemia) for thromboembolic events. Concomitant treatment with recombinant Factor VIIa likely increases the risk of developing a thromboembolic event. The risk of thrombotic and thromboembolic events may be increased with high doses of FEIBA.
The possible presence of such risk factors should always be considered in patients with congenital and acquired hemophilia.
FEIBA should be used with particular caution and only if there are no therapeutic alternatives in patients with an increased risk of thromboembolic complications. These include, but are not limited to, patients with a history of coronary heart disease, liver disease, DIC, arterial or venous thrombosis, post-operative immobilization, elderly patients and neonates.
Thrombotic microangiopathy (TMA) has not been reported in FEIBA clinical studies. Cases of TMAs were reported in an emicizumab clinical trial where subjects received FEIBA as part of a treatment regimen for breakthrough bleeding (see clinical discussion in the European Public Assessment Report (EPAR) of emicizumab; see also Oldenburg et al. Emicizumab Prophylaxis in Hemophilia A with Inhibitors. N Engl J Med 2017:377:809-818).
The safety and efficacy of FEIBA for breakthrough bleeding in patients receiving emicizumab has not been established.
Therefore, benefit-risk evaluation of FEIBA to be administered to emicizumab exposed patients is required, and patients must be closely monitored by their physicians (see also Interactions.)
If signs or symptoms of thrombotic and thromboembolic events are observed, the infusion should be stopped immediately and appropriate diagnostic and therapeutic measures initiated.
A single dose of 100 U/kg body weight and a daily dose of 200 U/kg body weight should not be exceeded unless the severity of bleeding warrants and justifies the use of higher doses. When used to stop bleeding, the product should be given only for as long as absolutely necessary to achieve the therapeutic goal.
Therapy monitoring: Individual doses of 100 U/kg body weight and daily doses of 200 U/kg body weight must not be exceeded. Patients receiving 100 U/kg body weight or more must be monitored carefully, particularly for the development of DIC and/or acute coronary ischemia and for symptoms of other thrombotic or thromboembolic events. High doses of FEIBA should be administered only as long as strictly necessary - in order to stop a hemorrhage.
If clinically significant changes in blood pressure or pulse rate, respiratory distress, coughing or chest pain occur, the infusion is to be discontinued immediately and appropriate diagnostic and therapeutic measures are to be initiated. Significant laboratory parameters for DIC are a drop in fibrinogen, a drop of the thrombocyte count and/or the presence of fibrin/fibrinogen degradation products (FDP). Other parameters for DIC are a clearly prolonged thrombin time, prothrombin time or aPTT. In patients with inhibitor hemophilia or with acquired inhibitors to factors VIII, IX and/or XI, the aPTT is prolonged by the underlying disease.
Patients with inhibitor hemophilia or with acquired inhibitors to coagulation factors, who are treated with FEIBA, may have increased bleeding tendency as well as increased risk of thrombosis at the same time.
Laboratory tests and clinical efficacy: In vitro tests, such as aPTT, whole blood coagulation time (WBCT) and thromboelastograms (TEG) as proof of efficacy do not have to correlate with the clinical picture. Therefore, attempts to normalize these values by increasing the dose of FEIBA cannot be successful, and are even to be strongly rejected because of the possible risk of triggering a DIC through overdosing.
Significance of the thrombocyte count: If the response to treatment with FEIBA is inadequate, conducting a thrombocyte count is recommended since a sufficient number of functionally intact thrombocytes is necessary for the efficacy of FEIBA.