FDA Greenlights Balfaxar for Warfarin Reversal

The US Food and Drug Administration (FDA) has approved Balfaxar (prothrombin complex concentrate, human-Ians) for the immediate reversal of acquired coagulation factor deficiency induced by vitamin K antagonist (such as warfarin) therapy in adult patients who need an urgent surgery or invasive procedures.

Balfaxar is a human plasma-derived, nonactivated four-factor prothrombin complex concentrate (4F-PCC) containing the coagulation factors II, VII, IX, and X and antithrombotic proteins C and S. It helps restore blood coagulation by replenishing the levels of clotting factors, which are deficient in patients undergoing warfarin therapy.

More than 2.4 million patients in the United States are prescribed warfarin to prevent the formation of blood clots after a heart attack, heart valve surgery, stroke, or deep vein thrombosis/pulmonary embolism, or from certain types of irregular heartbeat (eg, atrial fibrillation). The main side effect of warfarin is the increased risk of bleeding, particularly for patients undergoing urgent surgery or invasive procedures.

The approval was based on data from the phase 3, randomized, double-blind, noninferiority LEX-209 study, in which 208 patients were randomly assigned to receive a single dose of Balfaxar (n = 105) or Kcentra (control 4F-PCC; n = 103). At about 30 minutes post-infusion, 78.1% of patients who received Balfaxar achieved International Normalized Ratio (INR) of 1.5 or less compared with 71.8% of those who received Kcentra. None of the patients had their surgery canceled for inadequate INR correction.

Balfaxar dosing should be individualized on the basis of the patient’s INR value and body weight. Concurrent administration of vitamin K is recommended to maintain clotting factor levels once the effects of Balfaxar have diminished. The recommended dose in patients with pretreatment INR of 2 to 6 is 25, 35, and 50 International Units of factor IX per kilogram of body weight, respectively. The maximum dose of Balfaxar should not exceed 2500, 3500, and 5000 International Units.

The most common adverse events with Balfaxar were procedural pain, wound complications, asthenia, anemia, dysuria, procedural vomiting, and catheter site-related reactions. Monitoring patients for signs and symptoms of thromboembolic events is advised. It is contraindicated in patients who are allergic to heparin or have a history of heparin-induced thrombocytopenia and have an IgA deficiency with known antibodies against IgA.