Drug Interactions between fitusiran and Kogenate FS with Bioset

MONITOR: Although clotting factor concentrates (CFC) or bypassing agent (BPA) products are used in clinical practice to treat breakthrough bleeding in patients receiving fitusiran, coadministration of CFC or BPA products with fitusiran may have additive effects on thrombin generation and increase the risk of thrombosis. According to fitusiran product labeling, serious thrombotic events have been reported. Thrombotic events were reported in 2.6% of patients receiving the 80 mg once monthly dose, including a fatal event of cerebral venous sinus thrombosis. The 80 mg once monthly dose is not approved or recommended for use. Thrombotic events were reported in 1.4% of patients receiving fitusiran prophylaxis using the antithrombin-based dose regimen (AT-DR) that targeted antithrombin (AT) activity 15-35%.

MANAGEMENT: Caution and monitoring are recommended when fitusiran is used concomitantly with CFC or BPA products. The fitusiran product labeling states that after fitusiran is initiated, patients may continue their prior CFC or BPA prophylaxis for the first 7 days of treatment, but CFC or BPA prophylaxis should be discontinued no later than 7 days after the initial dose of fitusiran. If breakthrough bleeding occurs during the first 7 days after fitusiran initiation, manage the bleed using the patient's prior dosing regimen of CFC or BPA. If breakthrough bleeding occurs after 7 days from the first fitusiran dose, bleeds should be managed with a reduced dose and frequency of CFC or BPA to minimize the risk of thrombotic events. The recommended dose reductions are as follows:
For Factor VIII: Recommended dose is 10 units/kg, maximum dose is 20 units/kg. Repeat dosing should not occur less than 24 hours of initial dose.
For Factor IX (standard half-life): Recommended dose is 20 units/kg, maximum dose is 30 units/kg. Repeat dosing should not occur less than 24 hours of initial dose.
For Factor IX (extended half-life): Recommended dose is 20 units/kg, maximum dose is 30 units/kg. Repeat dosing should not occur less than 5 to 7 days of initial dose.
For Activated Prothrombin Complex Concentrate (aPCC): Recommended dose is 30 units/kg, maximum dose is 50 units/kg. Repeat dosing should not occur less than 24 hours of initial dose.
For Activated Recombinant Factor VII (rFVIIa): Recommended dose is 45 mcg/kg or less. Repeat dosing should not occur less than 2 hours of initial dose.
If adequate hemostatic control is not achieved, higher doses may be used based on clinical judgement.