General Information

Balfaxar (prothrombin complex concentrate, human-lans) is a blood coagulation factor replacement product.

Balfaxar is specifically indicated for the urgent reversal of acquired coagulation factor deficiency induced by Vitamin K antagonist (VKA, e.g., warfarin) therapy in adult patients with need for an urgent surgery/invasive procedure.

Dosing/Administration 

• Balfaxar is supplied as a lyophilized powder for solution, for intravenous use. 
• Balfaxar dosing should be individualized based on the patient’s baseline International Normalized Ratio (INR) value, and body weight. See table below.
• Administer Vitamin K concurrently to patients receiving Balfaxar to maintain factor levels once the effects of Balfaxar have diminished. 
• The safety and effectiveness of repeat dosing have not been established and it is not recommended.
• Administer reconstituted Balfaxar at a rate of 0.12 mL/kg/min (~3 units/kg/min) up to a maximum rate of 8.4 mL/min (~210 units/min)

Dosing is based on body weight. Dose based on actual potency is stated on the vial, which will vary from 20-32 Factor IX units/mL after reconstitution. The actual potency for a 500 unit vial ranges from 400-640 units/vial. The actual potency for a 1000 unit vial ranges from 800-1280 units/vial.

Mechanism of Action

The administration of Balfxar provides a rapid increase in plasma levels of the vitamin K-dependent coagulation factors (FII, FVII, FIX, FX) and antithrombotic proteins C and S. Together they are referred to/known as the prothrombin complex. Balfxar can temporarily correct the coagulation defect of patients with deficiency of one or several of these factors.

Side Effects

Adverse effects associated with the use of Balfxar may include, but are not limited to, the following:

• procedural pain
• wound complications
• asthenia
• anemia
• dysuria
• procedural vomiting
• catheter site related reaction

The Balfaxar drug label comes with the following Black Box Warning:

Patients being treated with Vitamin K antagonists (VKA) therapy have underlying disease states that predispose them to thromboembolic events. Potential benefits of reversing VKA should be weighed against the potential risks of thromboembolic events, especially in patients with the history of a thromboembolic event. Resumption of anticoagulation should be carefully considered as soon as the risk of thromboembolic events outweighs the risk of acute bleeding.

• Both fatal and non-fatal arterial and venous thromboembolic complications have been reported with Balfaxar in clinical trials and post marketing surveillance. Monitor patients receiving Balfaxar for signs and symptoms of thromboembolic events.
• Balfaxar may not be suitable in patients with thromboembolic events in the prior 3 months.

Clinical Trial Results

The FDA approval of Balfaxar was based on a head-to-head study comparing Balfaxar with a control 4F-PCC (Kcentra). The Phase III, randomized, double-blind, multicenter study was performed at 24 sites in the U.S. and Europe and randomized 208 patients to Balfaxar (N=105) or control 4F-PCC (N=103). Balfaxar met the primary endpoint of hemostatic efficacy and was non-inferior to the comparator, Kcentra, in patients on a vitamin K antagonist undergoing urgent surgery with significant bleeding risk. The primary objective was met at the prespecified interim analysis and the study was stopped due to statistically significant efficacy results. Balfaxar demonstrated effective hemostasis in 94.6% of patients versus 93.5% of patients for Kcentra. International Normalized Ratio (INR) reductions and vitamin K dependent coagulation factor increases supported the primary endpoint and PCC dosing and duration of infusion were also similar.