Factor VIII inhibitor bypassing fraction (Specialist drug)

UK SPC (FEIBA 100 u/ml powder and solvent for solution for infusion) section 4.2. SPECIALIST SUPERVISION: 'The treatment is to be initiated and monitored by a physician experienced in the treatment of coagulation disorders.' || GENERAL GUIDELINE, verbatim: 'As a general guideline, a dose of 50 - 100 U FEIBA per kg body weight is recommended; a single dose of 100 U/kg body weight and a maximum daily dose of 200 U/kg body weight must not be exceeded unless the severity of bleeding warrants and justifies the use of higher doses.' || SURGERY: 'In surgical interventions, an initial dose of 100 U/kg body weight may be administered preoperatively, and a further dose of 50 - 100 U/kg body weight may be administered after 6 - 12 hours. As a postoperative maintenance dose, 50 - 100 U/kg body weight may be administered at 6 - 12-hour intervals; dosage, dosage intervals and duration of the peri- and postoperative therapy are guided by the surgical intervention, the patient's general condition and the clinical efficacy in each individual case. (The maximum daily dose of 200 U/kg body weight must not be exceeded!)' || PROPHYLAXIS in haemophilia A patients with inhibitors: for patients with a high inhibitor titre and frequent haemorrhages after failed immune tolerance induction (ITI), or when ITI is not considered - 'A dose of 70 - 100 U/kg body weight every other day is recommended. If necessary, the dose may be increased to 100 U/kg body weight per day or it may be decreased gradually.' || DURING IMMUNE TOLERANCE INDUCTION: FEIBA may be administered concomitantly with factor VIII, 'in a dosage range of 50 - 100 U/kg body weight, twice per day, until the factor VIII inhibitor titre has decreased to < 2 B.U.' (1 Bethesda Unit is the amount of antibodies which inhibits 50% of factor VIII activity in incubated plasma, 2 h at 37 degrees C). || MONITORING LIMITATION, verbatim: 'In case of inadequate response to treatment with the product, it is recommended that a platelet count be performed because a sufficient number of functionally intact platelets are considered to be necessary for the efficacy of the product. Due to the complex mechanism of action, no direct monitoring of active ingredients is available. Coagulation tests such as the whole blood coagulation time (WBCT), the thromboelastogram (TEG, r-value) and the aPTT usually show only little reduction and do not necessarily correlate with the clinical efficacy. Therefore, these tests have little significance in the monitoring of the therapy with FEIBA.' || THROMBOSIS: section 4.4 records that thrombotic and thromboembolic events including DIC, venous thrombosis, pulmonary embolism, myocardial infarction and stroke have occurred, some of them with doses above 200 U/kg/day or in patients with other risk factors; concomitant recombinant factor VIIa likely increases the risk. Cases of thrombotic microangiopathy were reported in an emicizumab clinical trial where subjects received FEIBA for breakthrough bleeding. || TRUNCATION CAVEAT: sections 4.2, 4.3 and 4.6 were captured complete; section 4.4 was cut at the source-fetch limit part-way through the emicizumab/TMA paragraph and section 4.8's adverse-reaction table was cut in its footnotes, so the warnings and side-effect lists below are NOT complete.

dosePerKg is deliberately left null because the SPC gives no separate paediatric figure and the adult regimens are RANGES (50 to 100 U/kg) - do not let the weight calculator commit to one value. Section 4.2 verbatim: 'Paediatric population The experience in children under 6 years of age is limited; the same dose regimen as in adults should be adapted to the child's clinical condition.' The adult bleed-specific regimens above therefore apply, adapted clinically. Section 4.4 lists neonates among the patients at increased risk of thromboembolic complications, in whom FEIBA should be used with particular caution and only if there are no therapeutic alternatives. Verify against a children's formulary.