Unit dose formulation of antidotes for factor xa inhibitors and methods of using the same

Abstract

The present invention relates unit dose formulations of antidotes to anticoagulants targeting factor Xa. Disclosed herein are methods of stopping or preventing bleeding in a patient that is currently undergoing anticoagulant therapy with a factor Xa inhibitor.

1 . A unit dose formulation comprising a pharmaceutically acceptable carrier and from about 200 milligrams to about 1 gram of a two chain polypeptide comprising the amino acid sequence of SEQ ID NO. 13. 
     
     
         2 - 3 . (canceled) 
     
     
         4 . The unit dose formulation of  claim 1 , having from about 400 milligrams to about 900 milligrams of the polypeptide. 
     
     
         5 - 20 . (canceled) 
     
     
         21 . A method of preventing, reducing, or ceasing bleeding in a subject undergoing anticoagulant therapy with a factor Xa inhibitor comprising administering to the subject a unit dose formulation of  claim 1 . 
     
     
         22 - 24 . (canceled) 
     
     
         25 . The method of  claim 21 , wherein the unit dose formulation is administered intravenously by bolus. 
     
     
         26 . The method of  claim 21 , wherein the unit dose formulation is administered as an infusion or a combination of bolus plus infusion. 
     
     
         27 . The method of  claim 26 , wherein about 10 to about 20% of the formulation is administered as a bolus and the remaining formulation is infused over a period until bleeding has substantially ceased. 
     
     
         28 . The method of  claim 26 , wherein the formulation is administered for about 6 hours. 
     
     
         29 . The method of  claim 26 , wherein the formulation is administered for about 6 to about 12 hours. 
     
     
         30 . The method of  claim 26 , wherein the formulation is administered for about 12 to about 24 hours. 
     
     
         31 . The method of  claim 26 , wherein the formulation is administered for up to about 48 hours. 
     
     
         32 . A package or kit comprising a container containing a unit dose formulation comprising from about 200 milligrams to about 1 gram of a two-chain polypeptide comprising the amino acid sequence of SEQ ID NO. 13 and a package insert indicating that the unit dose formulation is suitable for preventing, reducing or ceasing bleeding in a human subject undergoing an anticoagulant therapy with a factor Xa (fXa) inhibitor, whether the fXa inhibitor is a direct fXa inhibitor or an indirect fXa inhibitor.